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Industrial Applications pp 165–194Cite as

Immunomodulators

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Part of the book series: The Mycota ((MYCOTA,volume 10))

Abstract

Fungal immunomodulators are high-value compounds in nutraceuticals and the high-value pharmaceutical market. Fungal immunosuppressors such as cyclosporins, mycophenolic acid and their derivatives are important medicines for the treatment of many diseases; and they are widely used as the main therapy for pre- and post-organ transplantation treatments to minimize the risk of the body’s rejection of the xenotransplanted organ. Further, fungal immunostimulators have a long history in nutraceuticals and preventive medicine through stimulation of the body defense mechanisms. However, most of the known immunostimulators were obtained from macrofungi (mushrooms). More recently, many fungal immunostimulators were used effectively to prevent and to treat many types of cancer. Thus, both the roles of immunosuppressor and immunostimulator are equally important. This chapter provides recent information regarding the chemistry, biosynthesis and industrial production of different types of fungal immunomodulators.

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References

  • Aarnio TH, Agathos SN (1990) Pigmented variants of Tolypocladium inflatum in relation to cyclosporine A production. Appl Microbiol Biotechnol 33:435--437

    Article  CAS  Google Scholar 

  • Abdel Fattah YR, El Enshasy H, Anwar M, Omar H, Abou El Magd E, Abou Zahra R (2007) Application of factorial experimental designs for optimization of cyclosporine A production by Tolypocladium inflatum in submerged culture. J Microbiol Biotechnol 17:1930–1936

    CAS  Google Scholar 

  • Abraham EP (1945) The effect of mycophenolic acid on the growth of Staphylococcus aureus in heart broth. Biochem J 39:398–404

    CAS  Google Scholar 

  • Adachi K, Chiba K (2007) FTY720 story. Its discovery and the following accelerated development of sphingosine 1-phosphate receptor agonists as immunomodulators based on reverse pharmacology. Perspect Med Chem 1:11–23

    Google Scholar 

  • Adachi K, Kohara T, Nakao N, Arita M, Chiba K, Mishina T, Sasaki S, Fujita T (1995) Design, synthesis, and structure–activity relationships of 2-substituted-2-amino-1,3-propanediols: discovery of a novel immunosuppressant, FTY720. Med Chem Lett 5:853–856

    Article  CAS  Google Scholar 

  • Adachi Y, Ohno N, Ohsawa M, Oikawa S, Yadomae T (1990) Change of biological activities of (1→3)-β-D-glucan from Grifola frondosa upon molecular-weight reduction by heat-treatment. Chem Pharmaceut Bull 38:477–481

    Article  CAS  Google Scholar 

  • Agathos SN, Lee J (1993) Mathematical modeling of the production of cyclosporine A by Tolypocladium inflatum: Effect of L-valine. Biotechnol Prog 9:54–63

    Article  CAS  Google Scholar 

  • Agathos SN, Marshall JW, Moraiti C, Parekh R, Madhosingh C (1986) Physiological and genetic factors for process development of cyclosporine fermentations. J Ind Microbiol 1:39–48

    Article  CAS  Google Scholar 

  • Agawal SS, Singh VK (1999) Immunomodulators: A Review of Studies on Indian Medicinal Plants and Synthetic Peptides. Proc Ind Natl Sci Acad B65:179–204

    Google Scholar 

  • Alani F, Grove J, Anderson WA, Moo-Young M (2009) Mycophenolic acid production in solid-state fermentation using a packed-bed bioreactor. Biochem Eng J 44:105–110

    Article  CAS  Google Scholar 

  • Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118

    Article  CAS  Google Scholar 

  • Alloway RR (1999) Generic immunosuppressant use in solid organ transplantation. Transplant Proc 31[Suppl 3A]:2S–5S

    Article  CAS  Google Scholar 

  • Alsberg CL, Black OF (1913) Contribution of the study of maize deterioration; biochemical and toxicological investigations of Penicillium puberulum and Penicillium stolonigerum. Bull Burl Anim Ind US Dept Agric 270:1–47

    Google Scholar 

  • Amano S, Ogawa N, Ohtsuka M, Ogawa S, Chida N (1998) Total synthesis and absolute configuration of FR65814. Chem Commun 1263–1264

    Google Scholar 

  • Amano S, Ogawa N, Ohtsuka M, Chida N (1999) Chiral and stereoselective total synthesis of novel immunosuppressant FR65814 from D-glucose. Tetrahedron 55:2205–2224

    Article  CAS  Google Scholar 

  • Anderson WK, Boehm TL, Makara GM, Swann TR (1996) Synthesis and modeling studies with monocyclic analogues of mycophenolic acid. J Med Chem 39:46–55

    Article  CAS  Google Scholar 

  • Ando K, Suzuki S, Tamaura G, Arima K (1968) Antiviral activity of mycophenolic acid. Studies on antiviral and antitumor antibiotic IV. J Antibiot 21:649–652

    Article  CAS  Google Scholar 

  • Appel GB, Radhakrishnan J, Ginzler EM (2005) Use of mycophenolate mofetil in autoimmune and renal diseases. Transplantation 80[Suppl]: S265–S271

    Article  CAS  Google Scholar 

  • Aw MM, Verma A, Rela M, Heaton N, Mieli-Vergani G, Dhawan A (2008) Long-term outcome of mycophenolate rescue therapy for resistant acute allograft rejection in pediatric liver transplant recipients. Liver Transplant 14:1303–1308

    Article  Google Scholar 

  • Balakrishnan K, Pandey A (1996) Influence of amino acids on the biosynthesis of cyclosporine A by Tolypocladium inflatum. Appl Microbiol Biotechnol 45:800–803

    Article  CAS  Google Scholar 

  • Banfi L, Beretta G, Colombo L, Gennari C, Scolastico C (1982) Total synthesis of (+)-thermozymocidin (myriocin) from D-fructose. J Chem Soc Chem Commun 488–490

    Google Scholar 

  • Bartman CD, Doerfler DL, Bird BA, Remaley AT, Peace JN, Campbell IM (1981) Mycophenolic acid production by Penicillium brevicompactum on solid media. Appl Env Microbiol 41:729–736

    CAS  Google Scholar 

  • Bedford CT, Knittel P, Money T, Phillips GT, Salisbury P (1973) Biosynthesis of mycophenolic acid. Can J Chem 51:694–697

    Article  CAS  Google Scholar 

  • Benedetti A, Colombo E, Nichele M, Pagani H (2002) Process for producing mizoribine by Eupenicillium javanicum. Patent EP 19990103099

    Google Scholar 

  • Bentley R (2000) Mycophenolic acid: a one hundred year odyssey from antibiotic to immunosuppressant. Chem Rev 100:3801–3825

    Article  CAS  Google Scholar 

  • Birch AJ, English RJ, Massy-Westropp RA, Smith H (1958) Studies in relation to biosynthesis. Part XIV. The origin of the nuclear methyl groups in mycophenolic acid. J Chem Soc 1958:365–368

    Article  Google Scholar 

  • Birkinshaw JH, Raistrick H, Ross DJ (1952) The molecular constitution of mycophenolic acid, A metabolic product of Penicilliusm brevicompactum Dierckx. Part 3. Further observations on the structural formula for mycophenolic acid. Biochem J 50:630–634

    CAS  Google Scholar 

  • Bissett J (1983) Notes on Tolypocladium and related genera. Can J Bot 61:1311–1329

    Article  Google Scholar 

  • Boiteau J-G, Van de Weghe P, Eustache J (2001) A new, ring closing metathesis-based synthesis of (–)-fumagillol. Org Lett 3:2737–2740

    Article  CAS  Google Scholar 

  • Borchers AT, Keen CL, Gerhwin ME (2004) Mushrooms, tumors, and immunity: an update. Exp Biol Med 229:393–406

    CAS  Google Scholar 

  • Budde K, Giessing M, Liefeldt L, Neumayer H-H, Glander P (2006) Moderne immunsuppressiva nach Nierentransplantation. Standard oder maßgeschneidert? Urologe 45:9–17

    Article  CAS  Google Scholar 

  • Butch AW (2008) Immunosuppressive drugs. In: Dasgupta A (ed) Handbook of drug monitoring methods. Humana, Totowa, pp 165–199

    Chapter  Google Scholar 

  • Carson CA, Kerr MA (2009) Total synthesis of FR901483. Org Lett 11:777–779

    Article  CAS  Google Scholar 

  • Carter SB, Franklin TJ, Jones DF, Leonard BJ, Mills SD, Turner RW, Turner WB (1969) Mycophenolic acid: An anti-cancer compound with unusual properties. Nature 223:848–850

    Article  CAS  Google Scholar 

  • Cattran DC, Wang MM, Appel G, Matalon A, Briggs W (2004) Mycophenolate mofetil in the treatment of focal segmental glomerulosclerosis. Clin Nephrol 62:405–411

    CAS  Google Scholar 

  • Chang H-H, Sheu F (2007) A novel fungal immunomodulatory protein (PCP) isolated from Poria cocos activates mouse peritoneal macrophage involved in toll-like receptor 4. FASEB J 21:702.15

    Google Scholar 

  • Chen L, Gao G, Felczak K, Bonnac L, Patterson SE, Wilson D, Bennett EM, Jayaram HN, Hedstrom L, Pankiewicz KW (2007) Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues. J Med Chem 50:5743–5751

    Article  CAS  Google Scholar 

  • Chen L, Wilson DJ, Labello NP, Jayaram HN, Pankiewicz KW (2008) Mycophenolic acid analoges with a modified metabolic profile. Bioorg Med Chem 16:9340–9345

    Article  CAS  Google Scholar 

  • Chen T-C, Wang T-S (2007) Use of fungal immunomodulatory protein. Patent EP 20060017781

    Google Scholar 

  • Chihara G (1992) Immunopharmacology of lentinan, a polysaccharide isolated from Lentinus edodes: Its application as a host defense potentiator. Int J Orient Med 17:57–77

    Google Scholar 

  • Chihara G, Hamuro J, Maeda Y, Arai Y, Fukuoka F (1970a) Antitumour polysaccharide derived chemically from natural glucan (pachyman). Nature 225:934–944

    Article  Google Scholar 

  • Chihara G, Hamuro J, Maeda YY, Arai Y, Fukuoka F (1970b) Fractionation and purification of the polysaccharides with marked antitumor activity, especially lentinan, from Lentinus edodes. Cancer Res 30:2776–2782

    CAS  Google Scholar 

  • Chun GT, Agathos SN (1989) Immobilization of Tolypocladium inflatum spores into porous celite beads for cyclosporine production. J Biotechnol 9:237–254

    Article  CAS  Google Scholar 

  • Cline JC, Nelson JD, Gerzon K, Williams RH, Delong DC (1969) In vitro antiviral activity of mycophenolic acid and its reversal by guanine compounds. Appl Microbiol 18:14–20

    CAS  Google Scholar 

  • Clutterbuck PW, Oxford AE, Raistrick H, Smith G (1932) Studies in the biochemistry of micro-organisms: the metabolite products of the Penicillium brevicompactum series. Biochem J 26:1441–1485

    CAS  Google Scholar 

  • Contreas M, DeSilva M (1994) The prevention and management of the hemolytic disease of newborn. J R Soc Med 87:256–258

    Google Scholar 

  • Covarrubias-Zúñiga A, González-Lucas A (1998) A total synthesis of mycophenolic acid. Tetrahedron Lett 39:2881–2882

    Article  Google Scholar 

  • Covarrubias-Zúñiga A, Gonzalez-Lucas A, Domínguez MM (2003) Total synthesis of mycophenolic acid. Tetrahedron 59:1989–1994

    Article  CAS  Google Scholar 

  • Cui FJ, Chisti Y (2003) Polysaccharopeptides of Coriolus versicolor: physiological activity, uses and production. Biotechnol Adv 21:109–122

    Article  CAS  Google Scholar 

  • Cui FJ, Li Y, Xu ZH, Sun K, Tao WY (2006) Optimization of the medium composition for production of mycelia biomass and exo-polymer by Grifola frondosa GF9801 using response surface methodology. Bioresour Technol 97:1209–1216

    Article  CAS  Google Scholar 

  • Cun Z, Mizuno T, Ito H, Shimura K, Sumiya T, Kawade M (1994) Antitumor activity and immunological property of polysaccharides from the mycelium of liquid-cultures Grifola frondosa. J Jpn Soc Food Sci Technol 41:724–733

    Article  Google Scholar 

  • Dittmann J, Wenger RM, Kleinkauf H, Lawen A (1994) Mechanism of cyclosporine A biosynthesis. Evidence for biosynthesis via a single linear undecapeptide precursor. J Biol Chem 269:2841–2846

    CAS  Google Scholar 

  • Doerfler DL, Nultron CP, Bartman CD, Gottlieb FJ, Campbell IM (1978) Spore germination, colony development, and secondary metabolism in Penicillium brevicompactum: a radiogas chromatographic and morphological study. Can J Microbiol 24:1490–1501

    Article  CAS  Google Scholar 

  • Doerfler DL, Bartman CD, Campbell IM (1979) Mycophenolic acid production by Penicillium brevicompacturm in two media. Can J Microbiol 25:940–943

    Article  CAS  Google Scholar 

  • Dreyfuss MM, Gams W (1994) Proposal to reject Pachybasium niveum Rostr. In order to retain the name Tolypocladium inflatum W. Gams for fungus that produces cyclosporin. Taxon 43:660–661

    Google Scholar 

  • El-Araby ME, Bernacki RJ, Makara GM, Pera PJ, Anderson WK (2004) Synthesis, molecular modeling, and evaluation of nonphenolic indole analogs of mycophenolic acid. Bioorg Med Chem 12:2867–2879

    Article  CAS  Google Scholar 

  • El Enshasy H (2007) Filamentous fungal cultures – process characteristics, products, and applications. In: Yang ST (ed) Bioprocessing for value-added products from renewable resources. Elsevier, Rotterdam, pp 225–261

    Chapter  Google Scholar 

  • El Enshasy H, Abdel Fattah Y, Atta A, Anwar M, Omar H, Abou EL Magd S, Abou Zahra R (2008) Kinetics of cell growth and cyclosporine A production by Tolypocladium inflatum when scaling up from shake flask to bioreactor. J Microbiol Biotechnol 18:913–917

    Google Scholar 

  • Engel G, von Milczewski EE, Prokopek D, Teuber M (1982) Strain-specific synthesis of mycophenolic acid by P. roqueforti in blue-veined cheese. Appl Env Microbiol 43:1034–1040

    CAS  Google Scholar 

  • Epinette WW, Parker CM, Jones EI, Greist MC (1987) Mycophenolic acid for psoriasis. J Am Acad Dermatol 17:962–971

    Article  CAS  Google Scholar 

  • Eugui EM, Allison AC (1993) Immunosuppressive activity of mycophenolic mofetil. Ann NY Acad Sci 685:309–329

    Article  CAS  Google Scholar 

  • Falch BH, Espevik T, Ryan L, Stokke BT (2000) The cytokine stimulating activity of (1→3)-β-D-glucans is dependent on the triple helix conformation. Carbohydr Res 329:587–596

    Article  CAS  Google Scholar 

  • Fan L, Soccol CR, Pandey A (2008) Mushroom production. In: Pandey A, Soccol CR, Larroche C (eds) Current developments in solid-state fermentation. Springer Science+Business Media, New York, pp 253–274

    Chapter  Google Scholar 

  • Ferraresso M, Kahan BD (1993) New immunosuppressive agents for pediatric transplantation. Pediatr Nephrol 7:567–573

    Article  CAS  Google Scholar 

  • Figg WD, Pluda JM, Lush RM, Saville MW, Wyvill K, Reed E, Yarchoan R (1997) The pharmacokinetics of TNP-470, a new angiogenesis inhibitor. Pharmacotherapy 17:91–97

    CAS  Google Scholar 

  • Foster BC, Coutts RT, Pasutto FM, Dossetor JB (1983) Production of cyclosporin A by carrageenan-immobilized Tolypocladium inflatum in an airlift reactor with external loop. Biotechnol Lett 5:693–696

    Article  CAS  Google Scholar 

  • Fuji K, Fujita E, Takaishi Y, Fujita T, Arita I, Komatsu M, Hirasuki N (1978) New antibiotics, trichopolyns A and B: isolation and biological activity. Experientia 34:237–239

    Article  CAS  Google Scholar 

  • Fujimoto H, Nakayama Y, Yamazaki M (1993) Identification of immunosuppressive components of musrhoom, Lactarius flavidulus. Chem Pharm Bull 41:654–658

    Article  CAS  Google Scholar 

  • Fujimoto H, Satoh Y, Yamazaki M (1998) Four new immunosuppressive components, kobiin and kobifuranones A, B, and C, from an ascomycetes, Gelasinospora kobi. Chem Pharm Bull 46:211–216

    Article  CAS  Google Scholar 

  • Fujino M, Li XK, Kitazawa Y, Guo L, Kawasaki M, Funeshima N, Amano T, Suzuki S (2002) Distinct pathways of apoptosis triggered by FTY720, etoposide, and anti-fas antibody in human T-lymphoma cell line (Jurkat cells). Pharmacol Exp Therap 300:939–945

    Article  CAS  Google Scholar 

  • Fujita T, Takaishi Y, Okamura A, Fujita E, Fuji K, Hirasuka N, Momatsu M, Arita I (1981) New peptide antibiotics, tricopolyns I and II from Trichoderma polysporum. J Chem Soc Chem Commun 585–587

    Google Scholar 

  • Fujita T, Inoue K, Yamamoto S, Ikumoto T, Sasaki S, Toyama R, Chiba K, Hoshino Y, Kumoto T (1994) Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot 47:208–215

    Article  CAS  Google Scholar 

  • Fujita T, Hamamichi N, Kiuchi M, Matsuzaki T, Kito Y, Inoue K, Hirose R, Yoneta M, Sasaki S, Chiba K (1996) Determination of absolute configuration and biological activity of new immunosuppresants, mycestericins D, E, F and G. J Antibiot 49:846–853

    Article  CAS  Google Scholar 

  • Gams W (1971) Tolypocladium. Eine Hyphomycetengattung mit geschwollenen Philaliden. Persoonia 6:185–191

    Google Scholar 

  • Gao Y, Zhou S (2003) Cancer prevention and treatment by Ganoderma, a mushroom with medicinal properties. Food Rev Int 19:275–325

    Article  Google Scholar 

  • Gao Y, Zhou S, Chen G, Dai X, Ye J (2003) A phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst. Extract (ganopoly) in patients with advanced cancer. Int J Med Mushroom 4:207–214

    Google Scholar 

  • Gong HG, Zhong JJ (2005) Hydrodynamic shear stress affects cell growth and metabolite production by medicinal mushroom Ganoderma lucidum. Chin J Chem Eng 13:426–428

    CAS  Google Scholar 

  • Gregory CR, Kyles AE, Bernsteen L, Wagner GS, Tarantal AF, Christe KL, Brignolo L, Spinner AG, Griffey SM, Paniagua RT, Hubble RW, Borie DC, Morris RE (2004) Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model. Transplantation 78:681–685

    Article  CAS  Google Scholar 

  • Gullo VP, McAlpine J, Lam KS, Baker W, Petersen F (2006) Drug discovery from natural products. J Ind Microbiol Biotechnol 33:523–531

    Article  CAS  Google Scholar 

  • Hartmann N, Enk A (2005) Mycophenolate mofetil and skin diseases. Lupus 14 [Suppl 1]:S58–S63

    Article  CAS  Google Scholar 

  • Hatanaka H, Kino T, Hashimoto M, Tsurumi Y, Kuroda A, Tanaka H, Goto T, Okuhara M (1988) FR65814, a novel immunosuppressant isolated from a Penicillium strain. J Antibiot 41:999–1008

    Article  CAS  Google Scholar 

  • Hayashi M, Kim YP, Takamatsu S, Preeprame S, Komiya T, Masuma R, Tanaka H, Komiyama K, Omura S (1996) Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. I. Taxonomy, fermentation, isolation and biological activities. J Antibiot 49:631–634

    Article  CAS  Google Scholar 

  • Hiestand, PC, Gunn H, Gale J (1985) The immunosuppressive profile of a new natural cyclosporine analogue: Nva2-cyclosporine. Transplant Proc 17:1362–1364

    CAS  Google Scholar 

  • Hiestand PC, Graber M, Hurtenbach V, Hermann P, Borel JF (1992) The new cyclosporine derivative, SDZ IMM 125: in vitro and in vivo pharmacological effects. Transplant Proc 24:31–38

    CAS  Google Scholar 

  • Hobbs C (2000) Medicinal values of Lentinus edodes (Berk.) Sing. (Agaricomyvetideae). A literature review. Int J Med Mushrooms 2:287–297

    Article  CAS  Google Scholar 

  • Hodge KT, Krasnoff SB, Humber RA (1996) “Tolypocladium inflatum is the anamorph of Cordyceps subsessilis”. Mycologia 88:715–719

    Article  Google Scholar 

  • Hoffmann K, Schneider-Scherzer E, Klein-Kauf H, Zocher R (1994) Purification and characterization of an eukaryotic alanine racemas, acting as a key enzyme in cyclosporine biosynthesis. J Biol Chem 269:12710–12714

    CAS  Google Scholar 

  • Hood KA, Zarembski DG (1997) Mycophenolate mofetil: a unique immunosuppressive agent. Am J Health Sys Pharm 54:285–294

    CAS  Google Scholar 

  • Hoppert M, Gentzsch C, Schörgendorfer K (2001) Structure and localization of cyclosporine synthetase, the key enzyme of cyclosporine biosynthesis in Tolypocladium inflatum. Arch Microbiol 176:285–293

    Article  CAS  Google Scholar 

  • Hsiao Y-M, Huang Y-L, Tang S-C, Shieh G-J, Lai J-Y, Wang H, Ying T-H, Ko J-L (2008) Effect of a fungal immunomodulatory protein from Ganoderma tsugae on cell cycle and interferon-gamma production through phosphatidylinositol 3-kinase signal pathway. Process Biochem 43:423–430

    Article  CAS  Google Scholar 

  • Hsu H-C, Hsu C-I, Lin R-H, Kao C-L, Lin J-Y (1997) Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella volvacea. Biochem J 323:557–565

    CAS  Google Scholar 

  • Iaccarino L, Rampudda M, Canova M, Della Libera S, Sarzi-Puttinic P, Doria A (2007) Mycophenolate mofetil: what is its place in the treatment of autoimmune rheumatic diseases? Autoimmun Rev 6:190–195

    Article  CAS  Google Scholar 

  • Iijima M, Masuda T, Nakamura H, Naganawa H, Kurasawa S, Okami Y, Ishizuka M, Takenchi T, Itaka Y (1992) Metacytofilin, a novel immunomodulator produced by Metarhizium sp. TA2759. J Antibiot 45:1553–1556

    Article  CAS  Google Scholar 

  • Ikekawa T, Uehara N, Maeda Y, Nakanish M, Fukuoka F (1969) Antitumor activity of aqueous extracts of edible mushrooms. Cancer Res 29:734–735

    CAS  Google Scholar 

  • Im D-S (2003) Linking Chinese medicine and G-protein-coupled receptors. Trends Pharmacol Sci 24:2–4

    Article  CAS  Google Scholar 

  • Iwabuchi Y, Furukawa M, Esumi T, Hatakeyama S (2001) An enantio- and stereocontrolled synthesis of (–)-mycestericin E via cimchona alkaloid-catalyzed asymmetric Baylis–Hillman reaction. Chem Comm (Comb) 19:2030–2031

    Article  CAS  Google Scholar 

  • Jaureguiberry G, Farragia-Fougerouse G, Audier H, Lederer E (1964) On transfer of the CD-3 group of methionine-CD-3 during biosynthesis of mycophenolic acid. CR Acad Sci Paris 259:3108–3110

    CAS  Google Scholar 

  • Jekkel A, Barta I, Kónya A, Sütő J, Boros S, Horváth G, Ambrus G (2001) Microbiological transformation of mycophenolic acid. J Mol Cat B Enz 11:423–426

    Article  CAS  Google Scholar 

  • Jekkel A, Barta I, Boros S, Sütő J, Horváth G, Szabó Z, Ambrus G (2002) Microbiological transformation of mycophenolic acid. Part II. J Mol Cat B Enz 19/20:209–214

    Article  Google Scholar 

  • Jones MC, Marsden SP (2008) Total synthesis of the immunosuppressants myriocin and 2-epi-myriocin. Org Lett 10:4125–4128

    Article  CAS  Google Scholar 

  • Jorgensen KA, Koefoed-Nielsen PB, Karamperis N (2003) Clacineurin phosphate activity and immunosuppression. A review on the role of calcineurin phosphate activity and the immunosppressive effect of cyclosporin A and tacrolimus. Scand J Immunol 57:93–98

    Article  CAS  Google Scholar 

  • Kahan BD (1992) New immunosuppressive drugs: needs in an applications to pediatric transplantation. Eur J Pediatr 151[Suppl 1]:S9–S12

    Article  Google Scholar 

  • Kallen J, Mikol V, Quesniaux VFJ, Walkinshaw MD, Schneider-Scherzer E, Schörgendorfer K, Weber G, Fliri HG (1997) Cyclosporins: Recent developments in biosynthesis, pharmacology and biology, and clinical applications. In: Rehm, H-J. and Reed G (eds) Biotechnology, VCH, Weinheim, pp 535–591

    Chapter  Google Scholar 

  • Kamigauchi T, Sakazaki R, Nagashima K, Kawamura Y, Yasuda Y, Matsushima K, Tani H, Takahashi Y, Ishii K, Suzuki R, Koizumi K, Nakai H, Ikenishi Y, Terui Y (1998) Terprenin, novel immunosuppressants produced by Aspergillus candidus. J Antibiot 51:445–450

    Article  CAS  Google Scholar 

  • Kawada K, Arimura K, Tsuri T, Fuji M, Komurasaki T, Yonezawa S, Kugimiya A, Haga N, Mitsumori S, Inagaki M, Nakatani T, Tamura Y, Takechi S, Taishi T, Kishino J, Ohtani M (1998) Total synthesis of terprenin, a highly potent and novel immunoglobulin E antibody suppressant. Ang Chem Int Ed 37:973–975

    Article  CAS  Google Scholar 

  • Kawagishi H, Nomura A, Mizuno T, Kimura A, Chiba S (1990) Isolation and characterization of lectin from Grifola frondosa fruiting bodies. Biochim Biophys Acta 1034:247–252

    Article  CAS  Google Scholar 

  • Khan MM (2008) Immunosuppressive agents. In: Khan MM (ed) Immunopharmacology Springer Science+Business Media, New York, pp 87–105

    Google Scholar 

  • Khedkar AP, Subramaniyam P, Ananda K, Ramkrishna M, Tambe SP, Ganesh S, Sircar A, Shrikumar S (2007) Manufacture and purification of cyclosporine A. US Patent 7,176,001

    Google Scholar 

  • Kida T, Takehiko I, Hiroshiro S (1984) Method for production of mycophenolic acid by fermentation. US Patent 4,452,891

    Google Scholar 

  • Kim D, Ahn SK, Bae H, Choi WJ, Kim HS (1997) An asymmetric total synthesis of (–)-fumagillol. Tetrahedron Lett 38:4437–4440

    Article  CAS  Google Scholar 

  • Kim D, Ahn SK, Bae H, Kim HS (2005a) A stereoselective asymmetric synthesis of antibiotic (–)-fumagillol using claisen rearrangement and intramolecular ester enolate alkylation as key steps. Arch Pharm Res 28:129–141

    Article  CAS  Google Scholar 

  • Kim F, Sakagami H, Tanuma SI, Konno K (1990) Stimulation of interferon-γ-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction. Anticancer Res 10:55–58

    CAS  Google Scholar 

  • Kim HM, Paik SY, Ra KS, Koo KB, Yun JW, Choi JW (2006) Enhanced production of exopolysaccharides by fed-batch culture of Ganoderma resinaceum DG-6556. J Microbiol 44:233–242

    CAS  Google Scholar 

  • Kim YO, Han SB, Lee HW, Ahn HJ, Yoon YD, Jung JK, Kim HM, Shin CS (2005b) Immuno-stimulating effect of the endo-polysaccharide produced by submerged culture of Inonotus obliquus. Life Sci 77:2438–2456

    Article  CAS  Google Scholar 

  • Kino K, Yamashita A, Yamaoka K, Watanabe J, Tanaka S, Ko K, Shimizu K, Tsunoo H (1989) Isolation and characterization of a new immunomodulatory protein, Ling Zhi-8 (LZ-8), from Ganoderma lucidium. J Biol Chem 264:472–478

    CAS  Google Scholar 

  • Klatt J, Hartung H-P, Hohlfeld R (2007) FTY720 (Fingolimod) als neue Therapiemöglichkeit der Multiplen Sklerose. Nervenarzt 78:1200–1208

    Article  CAS  Google Scholar 

  • Kluepfel D, Bagli J, Baker H, Charest M-P, Kudelski A, Sehgal SN, Vézina C (1972) Myriocin, a new antifungal antibiotic from Myriococcum albomyces. J Antibiot 25:109–115

    Article  CAS  Google Scholar 

  • Kluepfel D, Kudelski A, Bagli J (1975) Myriocin and process of preparation. US Patent 3,928,572

    Google Scholar 

  • Ko JL, Hsu CI, Lin RH, Kao CL, Lin JY (1995) A new fungal immunomodulatory protein, FIP-fve isolated from the edible mushroom, Flammulina velutipes and its complete amino acid sequence. Eur J Biochem 228:244–249

    Article  CAS  Google Scholar 

  • Kratochvil B, Jegorov A, Pakhomova S, Husák M, Bulej P, Cvak L, Sedmera P, Havlicek V (1999) Crystal structure of cyclosporine derivatives: O-acetyl-(4R)-4-(E-2-butyl)-4,N-dimethyl-L-threonyl-cyclosporin A and O-acetyl-(4R)-4-[E-2-(4-bromobutyl)]-4,N-dimethyl-L-threonyl-cyclosporin A. Collect Czec Chem Commun 64:89–98

    Article  CAS  Google Scholar 

  • Krishna C (2005) Solid-state fermentation systems – an overview. Crit Rev Biotechnol 25:1–30

    Article  CAS  Google Scholar 

  • Kroll M, Arenzana-Seisdedos F, Bachelerie F, Thomas D, Fringuet B, Conconi M (1999) The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome. Chem Biol 6:689–698

    Article  CAS  Google Scholar 

  • Kropf JF, Meigh IC, Bebbington MWP, Weinreb SM (2006) Studies on a total synthesis of the microbial immunosuppressive agent FR901483. J Org Chem 71:2046–2055

    Article  CAS  Google Scholar 

  • Kuboki H, Tsuchida T, Wakazono K, Isshik K, Kumagai H, Yoshioka T (1999) Mer-f3, 12-hydroxy-ovalicin, produced by Metarhizium sp. F3. J Antibiot 52:590–593

    Article  CAS  Google Scholar 

  • Kupfahl C, Ruppert T, Dietz A, Geginat G, Hof H (2007) Candida species fail to produce the immunosuppressive secondary metabolite gliotoxin in vitro. FEMS Yeast Res 7:986–992

    Article  CAS  Google Scholar 

  • Lafont P, Debeaupuis JP, Gaillardin M, Payen J (1979) Production of mycophenolic acid by Penicillium roqueforti strains. Appl Env Microbiol 37:365–368

    CAS  Google Scholar 

  • Lawen A, Zocher R (1990) Cyclosporin synthetase. The most complex peptide synthesizing multienzyme polypeptide so far described. J Biol Chem 256:11355–11360

    Google Scholar 

  • Lee J, Agathos SN (1989) Effect of amino acids on the production of cyclosporine A by Tolypocladium inflatum. Biotechnol Lett 11:77–82

    Article  CAS  Google Scholar 

  • Lee TH, Chun G-T, Chang YK (1997) Development of sporulation/immobilization method and its application for the continuous production of cyclosporin A by Tolypocladium inflatum. Biotechnol Prog 13:548–550

    CAS  Google Scholar 

  • Lee WA, Gu L, Miksztal AR, Chu N, Leung K, Nelson PH (1990) Bioavailability improvement of mycophenolic acid through amino ester derivatization. Pharm Res 7:161–166

    Article  CAS  Google Scholar 

  • Leung MY, Fung KP, Choy YM (1997) The isolation and characterization of an immunomodulatory and antitumor polysaccharide preparation from Flammulina velutipers. Immunopharmacol 35:255–263

    Article  CAS  Google Scholar 

  • Leung MYK, Liu C, Koon JCM, Fung KP (2006) Polysaccharide biological response modifiers. Immunol Lett 105:101–114

    Article  CAS  Google Scholar 

  • Licastro F, Morini MC, Kretz O, Dirheimer G, Creppy EE, Stirpe F (1993) Mitogenic activity and immunological properties of bolesatine, a lectin isolated from the mushroom Boletus satanas Lenz. Int J Biochem 25:789–792

    Article  CAS  Google Scholar 

  • Lida A, Mihara T, Fujita T, Takaishi Y (1999) Peptidic immunosuppressants from the fungus Trichoderma polysporum. Bioorg Med Chem Lett 24:3393–3396

    Google Scholar 

  • Lim JM, Yun JW (2006) Enhanced production of exopolysaccharides by supplementation of toluene in submerged culture of an edible mushroom Collybia maculate TG-1. Process Biochem 41:1620–1626

    Article  CAS  Google Scholar 

  • Lin WH, Hung CH, Hsu CI, Lin JY (1997) Dimerization of the N-terminal amphipathic alpha-helix domain of the fungal immunomodulatory protein from Ganoderma tsugae (Fip-gts) defined by yeast two hybrid system and site-directed mutagenesis. J Biol Chem 272:20044–20048

    Article  CAS  Google Scholar 

  • Lindequist U, Niedermeyer THJ, Jülich W-D (2005) The pharmaceutical potential of mushrooms. eCAM 2:285–299

    Google Scholar 

  • Liu C, Xie H, Su H, Han J, Liu Y (2003) Anti-thrombus effect on the fermented products of mycelium from Tremella aurantialba. Nat Prod Res Dev 3:35–37

    Google Scholar 

  • Liu F, Ooi VEC, Liu WK, Chang ST (1996) Immunomodulation and antitumor activity of polysaccharide–protein complex from culture filtrate of a local edible mushroom, Tricholoma lobayense. Gen Pharmacol 27:621–624

    Article  CAS  Google Scholar 

  • Liu J-K (2006) Natural terphenyls: developments since 1877. Chem Rev 106:2209–2223

    Article  CAS  Google Scholar 

  • Liu S, Widom J, Kemp CW, Crews CM, Clardy J (1998) Structure of human methionine aminopeptidase-2 complexed with fumagillin. Science 282:1324–1327

    Article  CAS  Google Scholar 

  • Liu V, Mackool BT (2003) Mycophenolate in dermatology. J Dermatol Treat 14:203–211

    Article  CAS  Google Scholar 

  • Logothetis CJ, Wu KK, Finn LD, Daliani D, Figg W, Ghaddar H, Gutterman JU (2001) Phase I trial of the angiogenesis inhibitor TNP-470 for progressive androgen-independent prostate cancer. Clin Cancer Res 7:1198–1203

    CAS  Google Scholar 

  • Loosli HR, Oschkinat H, Weber HP, Petcher T (1985) The conformation of cyclosporine A in the crystal and in solution. Helv Chim Acta 69:682–704

    Article  Google Scholar 

  • Lowe E, Rice P, Ha TZ, Li CF, Kelley J, Ensley H, Lopez-Perez J, Kalbfleisch J, Lowman D, Margl P, Browder W, Williams D (2001) A (1→3)-β-D-linked heptasaccharide is the unit ligand for glucose pattern recognition receptors on human monocytes. Microbes Infect 3:789–797

    Article  CAS  Google Scholar 

  • Lull C, Wichers HJ, Savelkoul HFJ (2005) Antiinflammatory and immunomodulating properties of fungal metabolites. Mediat Inflam 2:63–80

    Article  Google Scholar 

  • Ly M, Margaritis A (2007) Effect of temperature on the extraction kinetics and diffusivity of cyclosporine A in the fungus Tolypocladium inflatum. Biotechnol Bioeng 96:945–955

    Article  CAS  Google Scholar 

  • Ly M, Margaritis A, Jajuee B (2007) Effect of solvent concentration on the extraction kinetics and diffusivity of cyclosporine A in the fungus. Tolypocladium inflatum. Biotechnol Bioeng 96:67–79

    Article  CAS  Google Scholar 

  • Mao XB, Zhong JJ (2004) Hyperproduction of corydycepin by two-stage dissolved oxygen control in submerged cultivation of medicinal mushroom Cordyceps militaris in bioreactors. Biotechnol Prog 20:1408–1413

    Article  CAS  Google Scholar 

  • Mao XB, Zhong JJ (2006) Significant effect of NH4 + on cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Enz Microb Technol 38:343–350

    Article  CAS  Google Scholar 

  • Marahiel MA, Stachelhaus T, Mootz HD (1997) Modular peptide synthetases involved in non-ribosomal synthesis. Chem Rev 97:2651–2673

    Article  CAS  Google Scholar 

  • Matsuzawa Y, Nakase T (1984) Metabolite fate of ethyl O-[N-(p-carboxyphenyl)-carbamoyl] mycophenolate (CAM), a new antitumor agent, in experimental animals. J Pharmacobiodyn 7:776–783

    Article  Google Scholar 

  • Mazitschek R, Huwe A, Giannis A (2005) Synthesis and biological evaluation of novel fumagillin and ovalicin analogues. Org Biomol Chem 3:2150–2154

    Article  CAS  Google Scholar 

  • McCorkindale NJ Baxter RL (1981) 4-methyl- and 7-methylphthalan-1-one derivatives of mycophenolic acid: use in establishing the distribution of acetate derived hydrogens. Tetrahedron 37:2131–2136

    Article  Google Scholar 

  • Menza-Aviña ME, Ordoñez M, Fernández-Zertuche M, Rodriguez-Fragoso L, Esparza JR, de los Ríos-Corsino AAM (2005) Synthesis of some monocyclic analogues of mycophenolic acid via the Johnson ortho ester Claisen rearrangement. Bioorg Med Chem 13:6521–6528

    Article  CAS  Google Scholar 

  • Mi-Jin L, Duong CTP, Han K, Kim E-S (2009) Combination strategy to increase cyclosporin A productivity by Tolypocladium niveum using random mutagenesis and protoplast transformation. J Microbiol Biotechnol 19:869–872. doi: 10.4014/jmb.0811.629

    Article  CAS  Google Scholar 

  • Mimura H, Ohno N, Suzuki I, Yadomae T (1985). Purification, antitumor activity, and structural characterization of β-1,3-glucan from Peziza versiculosa. Chem Pharm Bull 33:5096–5099

    Article  CAS  Google Scholar 

  • Mitsui H, Matsuno T, Ogawa H, Shiio T, Yugari Y, Tamura G (1981) Antitumor activity of a new compound, ethyl O-[N-(p-carboxyphenyl)-carbamoyl]-mycophenolate, against various experimental tumors upon oral administration. Gann 72:66–71

    CAS  Google Scholar 

  • Miyake Y, Kozutsumi Y, Nakamura S, Fujita T, Kawasaki T (1995) Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin. Biochem Biophys Res Commun 211:396–403

    Article  CAS  Google Scholar 

  • Miyazaki T, Nishijima M (1981) Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum. Chem Pharm Bull 29:3611–3625

    Article  CAS  Google Scholar 

  • Mizobuchi M, Iwasaki Y, Sako K, Kaneko Y (1997) Suppression of acute experimental allergic encephalomyelitis in Lewis rats with a mycophenolic acid derivative. Tohoku J Exp Med 182:217–229

    Article  CAS  Google Scholar 

  • Mizuno K, Tsujino M, Takada M, Hayashi M, Atsumi K, Asano K, Matsuda T (1974) Studies on bredinin, I. Isolation, characterization and biological properties. J Antibiot 27:775–782

    CAS  Google Scholar 

  • Mizuno K, Takuji A, Masatoshi T, Masaki T, Munetoshi Y, Tetsuo M, Mitsuo H (1975) 4-Carbamoyl-1-β-D-ribofuranosylimidazolium-5-olate. US Patent 3,888,843

    Google Scholar 

  • Mizuno T (1992) Antitumor active polysaccharides isolated from the fruiting body of Hericium erinaceum, and edible, and medicinal mushroom called Yamabushitake or Houtou. Biosci Biotechnol Biochem 56:349–357

    Article  Google Scholar 

  • Molino BF, Yang Z (2006) Novel cyclosporine analogues and their pharmaceutical uses. US Patent 2006/0069015 A1

    Google Scholar 

  • Moradali M-F, Mostafavi H, Chods S, Hedjaroude G-A (2007) Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi). Int Immunopharmacol 7:701–724

    Article  CAS  Google Scholar 

  • Moussaïf M, Jacques P, Schaarwächter P, Budzikiewicz H, Thonart P (1997) Cyclosporin C is the main antifungal compound produced by Acremonium luzulae. Appl Environ Microbiol 63:1739–1743

    Google Scholar 

  • Muth WL, Nash III CH (1975) Biosynthesis of mycophenolic acid: purification and characterization of S-adenosyl-L-methionine: Demethylmycophenolic acid O-methyltransferase. Antimicrob Agents Chemother 8:321–327

    Article  CAS  Google Scholar 

  • Mydlarski PR (2005) Mycophenolate mofetil: a dermatologic perspective. Skin Ther Lett 10:1–6

    CAS  Google Scholar 

  • Nakajima S, Nozawa K (1979) Isolation in high yield citrinin from Penicillium odoratum and of mycophenolic acid from Penicillium brunneostoloniferum. J Nat Prod 42:423–426

    Article  CAS  Google Scholar 

  • Nakajima H, Hasasaki T, Tanaka K, Kimura Y, Udagawa S-I, Horie Y (1989) Production of cyclosporine by fungi belonging to the genus Neocosmospora. Agric Biol Chem 53:2291–2292

    Article  CAS  Google Scholar 

  • Nawata Y, Kuriki Y, Haneda M, Ochi K, Mori T (1988) Structure of a mycophenolic acid derivative (CAM). Acta Cryst C44:196–198

    CAS  Google Scholar 

  • Nawata Y, Kuriki Y, Haneda M, Ochi K, Mori T (1989) Crystal structure of a mycophenolic acid derivative, CAM (form Ia). Anal Sci 5:119–120

    Article  CAS  Google Scholar 

  • Nelson PH, Eugul E, Wang CC, Allison AC (1990) Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid. J Med Chem 33:833–838

    Article  CAS  Google Scholar 

  • Nelson PH, Carr SF, Devens BH, Eugui EM, Franco F, Gonzalez C, Hawley RC, Loughhead DG, Milan DJ, Papp E, Patterson JW, Rouhafza S, Sjogren EB, Smith DB, Stephenson RA, Talamas FX, Waltos A-M, Weikert RJ, Wu JC (1996) Structure–activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid. J Med Chem 39:4181–4196

    Article  CAS  Google Scholar 

  • Niido O, Suzuki Y, Yoshimaru T, Inoue T, Takayama T, Ra C (2006) Fungal metabolite gliotoxin blocks mast cell activation by a calcium- and superoxide-dependent mechanism: implications of immunosuppressive activities. Clin Immunol 118:108–116

    Article  CAS  Google Scholar 

  • Nulton CP, Campbell IM (1977) Mycophenolic acid is produced during balanced growth of Penicillium brevicompactum. Can J Microbiol 23:20–27

    Article  CAS  Google Scholar 

  • Nulton CP, Campbell IM (1978) Labelled acetone and levulinic acid are formed when [14C]acetate is being converted to mycophenolic acid in Penicillium brevicompactum. Can J Microbiol 24:1999–2001

    Article  Google Scholar 

  • Offenzeller M, Su Z, Santer G, Moser H, Traber R, Memmert K, Schneider-Scherzer E (1993) Biosynthesis of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine of cyclosporine A. Identification of 3(R)-hydroxy-4(R)-methyl-6(E)-octenoic acid as a key intermediate by enzymatic in vitro synthesis and by in vivo labelling techniques. J Biol Chem 268:26127–26134

    CAS  Google Scholar 

  • Ohno N, Miura NN, Chiba N, Adachi Y, Yadomae T (1995) Conparison of the immunopharmacological activities of triple and single-helical schizophyllan in mice. Biol Pharmaceut Bull 18:1242–1247

    Article  CAS  Google Scholar 

  • Oishi T, Ando K, Inomiya K, Sato H, Iida M, Chida N (2002) Total synthesis of (+)-myriocin and (–)-sphingofungin E from aldohexoses using overman rearrangement as the key reaction. Bull Chem Soc Jpn 75:1927–1947

    Article  CAS  Google Scholar 

  • Ooi VEC (2008) Antitumor and immunomodulatory activities of mushroom polysaccharides. In: Cheung PCK (ed) Mushrooms as functional food. Wiley, Singapore, pp 147–198

    Chapter  Google Scholar 

  • Ooi VEC, Liu F (2000) Immunomodulation and anti-cancer activity of polysaccharide-protein complex. Curr Med Chem 7:715–729

    Article  CAS  Google Scholar 

  • Ozaki H, Ishihara M, Kida T, Yamanaka S, Shibai H (1987a) Mycophenolic acid production by drug-resistant and methionine or glutamic-acid requiring mutants of Penicillium brevicompactum. Agric Biol Chem 51:2509–2514

    Article  CAS  Google Scholar 

  • Ozaki H, Kubota K, Takahashi H (1987b) Effects various adsorbents on mycelium formation and mycophenolic acid production by Penicillium brevicompactum. Agric Biol Chem 51:2503–2508

    Article  CAS  Google Scholar 

  • Pahl HL, Krauβ B, Schulze-Osthoff K, Decker T, Traenckner EBM, Vogt M, Myers C, Parks T, Warring P, Mühlbacher A, Czernilofsky A-P, Baeuerle PA (1996) The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-κB. J Exp Med 183:1829–1840

    Article  CAS  Google Scholar 

  • Palleschi A, Bocchinfuso G, Coviello T, Alhaique F (2005) Molecular dynamics investigations of the polysaccharide sclera-glucan: first study on the triple helix structure. Carbohydr Res 340:2154–2162

    Article  CAS  Google Scholar 

  • Patel J, Kobashigawa JA (2008) Minimization of immunosuppression transplant immunology. Transplant Immunol 20:38–54

    Article  CAS  Google Scholar 

  • Patterson JW (1993) The synthesis of mycophenolic acid. Tetrahedron 49:4789–4798

    Article  CAS  Google Scholar 

  • Pirofski L-A, Casadevall A (2006). Immunomodulators as an antimicrobial tool. Curr Opin Microbiol 9:489–495

    Article  CAS  Google Scholar 

  • Plé PA, Hamon A, Jones, G (1997) A convergent synthesis of mycophenolic acid. Tetrahedron 53:3395–3400

    Article  Google Scholar 

  • Preddie DC, Markowitz GS, Radhakrishnan J, Nickolas TL, D’Agati VD, Schwimmer JA, Gardenswartz M, Rosen R, Appel GB (2006) Mycophenolate mofetil for the treatment of interstitial nephritis. Clin J Am Soc Nephrol 1:718–722

    Article  CAS  Google Scholar 

  • Puel O, Tadrist S, Galtier P, Oswald I, Delaforge M (2005) Byssochlamys nivea as a source of mycophenolic acid. Appl Environ Microbiol 71:550–553

    Article  CAS  Google Scholar 

  • Queener SW, Nash III CH (1978) Procedure for obtaining Penicillium species mutants with improved ability to synthesize mycophenolic acid. US Patent 4,115,197

    Google Scholar 

  • Queener SW, Wilkerson SG, Nash III CH (1982) Sterol content and titer of mycophenolic acid in polyene antibiotic resistant mutants of Penicillium stoloniferum. In: Krumphabzl V, Sikyta B, Vanek Z (eds) Overproduction of microbial products. Academic, New York, pp 535–548

    Google Scholar 

  • Ren Y, Strobel GA, Graff JC, Jutila M, Park SG, Gosh S, Teplow D, Condron M, Pang E, Hess WM, Moore E (2008) Colutellin A, an immunosuppressive peptide from Colletotrichum dematium. Microbiology 154:1973–1979

    Article  CAS  Google Scholar 

  • Research and Markets (2007) http://www.researchandmarkets.com/reports/573667. Accessed 20 May 2009

  • Reshetnikov SV, Wasser SP, Tan KK (2001) Higher basidiomycetes as a source of antitumor and immunostimulating polysaccharides. Int J Med Mushrooms 3:361–394

    CAS  Google Scholar 

  • Roh YT (2008) Process for mass production of mycophenolic acid by using urea as nitrogen source. Patent WO 2008/026883 A1

    Google Scholar 

  • Rohloff JC, Gardner JO, Towne RW (1995) Mycophenolate dianions. Tetrahedron Lett 43:7803–7806

    Article  Google Scholar 

  • Russell R, Paterson M (2008) Cordyceps – a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry 69:1469–1495

    Article  CAS  Google Scholar 

  • Sadhukhan AK, Murthy MVR, Kumar RA, Mohan EVS, Vandana G, Bhar C, Rao KV (1999) Optimization of mycophenolic acid production in solid state fermentation using response surface methodology. J Ind Microbiol 22:33–38

    Article  CAS  Google Scholar 

  • Sakai J-I, Kezuka T, Yokoi H, Okada AA, Usui M, Mizuguchi J, Kaneko Y (1999) Suppressive effects of a novel compound on interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis in rats. Allergol Int 48:189–197

    Article  CAS  Google Scholar 

  • Sakamoto K, Tsujii E, Abe F, Nakanishi T, Yamashita M, Shigematsu N, Izumi S, Okuhara M (1996) FR901483, a novel immunosuppressant isolated from Cladobotryum sp. No. 11231. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological activities. J Antibiot 49:37–44

    Article  CAS  Google Scholar 

  • Sanchis V, Scott PM, Farber JM (1988) Mycotoxin-producing potential of fungi isolated from red kidney beans. Mycopathologia 104:157–162

    Article  CAS  Google Scholar 

  • Sarangi I, Ghosh D, Bhutia SK, Mallick SK, Maiti TK (2006) Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int Immunopharmacol 6:1287–1297

    Article  CAS  Google Scholar 

  • Sasaki S, Hashimoto R, Kiuchi M, Inoue K, Ikumoto T, Hirose R, Chiba K, Hoshino Y, Okumoto T, Fujita T (1994) Fungal metabolites. Part 14. Novel potent immunosuppressants, mycestericins, produced by Mycelia sterilia. J Antibiot 47:420–433

    Article  CAS  Google Scholar 

  • Sasaki T, Takasuka N, Chihara G, Maeda YY (1976) Antitumor activity of degraded products of lentinan – its correlation with molecular weight. Gann 67:191–195

    CAS  Google Scholar 

  • Sato H, Sato K, Iida M, Yamanaka H, Oishi T, Chiba N (2008) Total synthesis of mycestericin A. Tetrahedron Lett 49:1943–1947

    Article  CAS  Google Scholar 

  • Sawada H, Kaihara S, Egawa H, Inomata Y, Tanaka K, Yamaoka Y (1996) Efficacy of a new immunosuppressant, CAM, on small bowel transplantation in rats. Transplant Proc 28:2512–2513

    CAS  Google Scholar 

  • Sawai K, Okuno T, Terada Y, Harada Y, Sawamura K, Sasaki H, Takao S (1981) Isolation and properties of two antifungal substances from Fusarium solani. Agric Biol Chem 45:1223–1228

    Article  CAS  Google Scholar 

  • Schneweis I, Meyer K, Hörmansdorfer S, Bauer J (2000) Mycophenolic acid in silage. Appl Environ Microbiol 66:3639–3641

    Article  CAS  Google Scholar 

  • Schreiber SL Crabtree GR (1992) The mechanism of action of cyclosporine A and FK-506. Immunol Today 13:1–15

    Article  Google Scholar 

  • Seidel G, Laurich D, Fürstner A (2004) Iron-catalyzed cross-coupling reactions. A scalable synthesis of the immunosuppressive agent FTY720. J Org Chem 69:3950–3952

    Article  CAS  Google Scholar 

  • Sekar C, Balaraman K (1998a) Immobilization of the fungus, Tolypocladium sp. for the production of cyclosporine A. Bioproc Eng 18:281–283

    Article  Google Scholar 

  • Sekar C, Balaraman K (1998b) Optimization studies on the production of cyclosporine A by solid state fermentation. Bioproc Eng 18:293–296

    Article  CAS  Google Scholar 

  • Sekar C, Rajasekar VW, Balaraman K (1997) Production of cyclosporine A by solid state fermentation. Bioproc Eng 17:257–259

    Article  CAS  Google Scholar 

  • Senn H, Weber C, Kobel H, Traber R (1991) Selective 13C-labelling of cyclosporine A. Eur J Biochem 199:653–658

    Article  CAS  Google Scholar 

  • She QB, Ng TB, Liu WK (1998) A novel lectin with potent immunomodulatory activity isolated from both fruiting bodies and cultured mycelia of the edible mushroom Volvariella volvacea. Biochem Biophys Res Comm 247:106–116

    Article  CAS  Google Scholar 

  • Shibasaki F, Hallin U, Uchino H (2002) Calcineurin as a multifunctional regulator. J Biochem (Tokyo) 131:1–15

    Article  CAS  Google Scholar 

  • Shumpei Y (2002). Mizoribine: mode of action and effects in clinical use. Pediatrics Int 44:196–198

    Article  Google Scholar 

  • Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH (1989) A cytosolic binding protein for the immunosuppressant FK506 has peptidylprolyl isomerase activity but is distinct from cyclophilin. Nature 341:755–757

    Article  CAS  Google Scholar 

  • Sigg HP, Weber HP (1968) Isolierung und Strukturaufklärung von Ovalicin. Helv Chim Acta 51:1395–1408

    Article  CAS  Google Scholar 

  • Sintchak MD, Fleming MA, Futer O, Raybuck SA, Chambers SP, Caron PR, Murcko MA, Wilson KP (1996) Structure and mechanism of inosine monophosphate dehydrogenase in complex with immunosuppressant mycophenolic acid. Cell 85:921–930

    Article  Google Scholar 

  • Sircar A, Suryanarayan S, Khedkar AP, Subramaniyam P, Tamber SP (2005) Manufacture and purification of mycophenolic acid. US Patent 6,927,047

    Google Scholar 

  • Smith JE, Rowan NJ, Sullivan R (2002) Medicinal mushrooms: a rapidly developing area of biotechnology for cancer therapy and other bioactivities. Biotechnol Lett 24:1839–1845

    Article  CAS  Google Scholar 

  • Spatz S, Rundnicka A, McDonald C (1978) Mycophenolic acid in psoriasis. Br J Dermatol 98:429–434

    Article  CAS  Google Scholar 

  • Sugito K, Koshinaga T, Inoue M, Ikeda T, Hagiwara N, Fukuzawa M (2005) The effect of a novel immunosuppressant, FTY720, in mice without secondary lymphoid organs. Surg Today 35:662–667

    Article  CAS  Google Scholar 

  • Survase SA, Saudagar PS, Bajaj IB, Singhal RS (2007) Scleroglucan: fermentative production, downstream processing and applications. Food Technol Biotechnol 45:107–118

    CAS  Google Scholar 

  • Svarstad H, Bugge HC, Dhillion SS (2000) From Norway to Novartis: cyclosporine from Tolypocladium inflatum in an open access bioprospecting regime. Biodiv Conserv 9:1521–1541

    Article  Google Scholar 

  • Takahashi A, Kusano G, Ohta T, Nozoe S (1988) The constituents of Lactarius flavidulus Imai. Chem Pharm Bull 36:2366–2370

    Article  CAS  Google Scholar 

  • Takahashi A, Kusano G, Ohta T, Nozoe S (1993) Revised structures of flavidulos, constituents of Lactarius flavidulus Imai, and the structure of flavidulol D. Chem Pharm Bull 41:2032–2033

    Article  CAS  Google Scholar 

  • Takazawa K, Hosoda Y, Bashuda H, Yagita H, Okumura K, Kaneko Y (1995) CAM – a novel immunosuppressive agent. Transplant 59:1723–1727

    Article  CAS  Google Scholar 

  • Takei S (2002) Mizoribine in the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Pediatr Int 44:205–209

    Article  CAS  Google Scholar 

  • Tanaka E, Inoue E, Kawaguchi Y, Tomatsu T, Yamanaka H, Hara M, Kamatani N (2006) Acceptability and usefuleness of mizoribine in the management of rheumatoid arthritis in methotrexate-refractory patients and elderly patients, based on analysis of data from a large-scale observational cohort study. Mod Rheumatol 16:214–219

    Article  CAS  Google Scholar 

  • Tang YJ, Zhong JJ (2003) Role of oxygen supply in submerged fermentation of Ganoderma lucidum for production of Ganoderma polysaccharide and ganoderic acid. Enz Microb Technol 32:478–484

    Article  CAS  Google Scholar 

  • Tang YJ, Zhu LW, Li HM, Li DS (2007) Submerged culture of mushrooms in bioreactors – challenges, current state-of-the-art, and future prospects. Food Technol Biotechnol 45:221–229

    CAS  Google Scholar 

  • Tao Y, Zhang L, Cheung PCK (2006) Physicochemical properties and antitumor activities of water soluble native and sulfated hyperbranched mushroom polysaccharides. Cabohydr Res 341:2261–2269

    Article  CAS  Google Scholar 

  • Tiwari S, Sathyanathan D, Thomas E, Melarkode R, Ramavana G, Suryanaraya S (2003) Fed batch solid state fermentation for the production of mycophenolic acid. Patent WO/2003/106690

    Google Scholar 

  • Tönshoff B (2006) Mycophenolsäure nach Nierentransplantation. Nephrologe 1:59–61

    Article  Google Scholar 

  • Traber R, Loosli HR, Hofmann HR (1982) Isolierung und Strukturermittlung der neuen Cyclosporine E, F, G, H und I. Helv Chem Acta 65:1655–1677

    Article  CAS  Google Scholar 

  • Traber R, Hoffmann H, Lossli HR (1987) Neue Cyclosporine aus Tolypocladium inflatum. Die Cyclosporine K–Z. Helv Chem Acta 70:13–36

    Article  CAS  Google Scholar 

  • Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, Orita K (1984) Krestin (PSK).Cancer Treat Rev 11:131–155

    Article  CAS  Google Scholar 

  • Turk BE, Su Z, Liu JO (1998) Synthetic analogues of TNP-470 and ovalicin reveal a common molecular basis for inhibition of angiogenesis and immunosuppression. Bioorg Med Chem 6:1163–1169

    Article  CAS  Google Scholar 

  • Uchida K, Tominaga Y, Haba T, Katayama A, Matsuoka S, Goto N, Ueki T, Kimata T, Takeda A, Morozumi K, Takagi H, Nakao A (2004) Clinical success of NEORAL absorption profile. Transplant Proc 36[Suppl 2S]:S461–S464

    Article  CAS  Google Scholar 

  • Van der Hem LG, van der Vliet JA, Kino K, Hoitsma AJ, Tax WJM (1996) Ling Zhi-8: A fungal protein with immunomodulatory effects. Transplant Proc 28:958–959

    CAS  Google Scholar 

  • Velkov T, Lawen A (2003) Non-ribosomal peptide synthetases as technological platforms for the synthesis of highly modified peptide bioeffectors – cyclosporin synthetase as a complex example. Biotechnol Annu Rev 9:151–197

    Article  CAS  Google Scholar 

  • Velkov T, Singaretnam LG, Lawen A (2006) An improved purification procedure for cyclosporine synthetase. Protein Express Purific 45:275–287

    Article  CAS  Google Scholar 

  • Vinokurova N, Ivanushkina N, Kochkina G, Arinbasarov M, Ozerskaya S (2005) Production of mycophenolic acid by fungi of genus Penicillium link. Appl Biochem Microbiol 41:83–86

    Article  CAS  Google Scholar 

  • Von Arx JA (1986) Tolypocladium, a synonym of Beauveria. Mycotaxon 25:153–158

    Google Scholar 

  • Vonderscher J, Meinzer A (1994) Rationale for the development of Sandimmune Neoral. Transplant Proc 26:2925–2927

    CAS  Google Scholar 

  • Wang HX, Liu WK, Ng TB, Ooi VEC, Chang ST (1996) The immunomodulatory and antitumor activities of lectins from mushroom Tricholoma mongolicum. Immunopharmacology 31:205–211

    Article  CAS  Google Scholar 

  • Wang HX, Ng TB, Ooi VEC, Liu WK, Chang ST (1997) Actions of lectins from the mushroom Tricholoma mongolicum on macrophages, splenocytes and life-span in sarcoma-bearing mice. Anticancer Res 17:419–424

    CAS  Google Scholar 

  • Wang HX, Gao J, Ng TB (2000) A new lectin with highly potent antihepatoma and antisarcoma activities from the oyster mushroom Pleurotus ostreatus. Biochem Biophys Res Comm 275:810–816

    Article  CAS  Google Scholar 

  • Wang JC, Hu SH, Liang ZC, Yeh CJ (2005) Optimization for the production of water-soluble polysaccharide from Pleurotus citrinopileatus in submerged culture and its antitumor effect. Appl Microbiol Biotechnol 67:759–766

    Article  CAS  Google Scholar 

  • Wang P-H, Hsu C-I, Tang SC, Huang Y-L, Lin J-Y, Ko J-L (2004) Fungal immunomodulatory protein from Flammulina velutipes induces interferon-γ production through p38 mitogen-activated protein kinase signaling pathway. Agric Food Chem 52:2721–2725

    Article  CAS  Google Scholar 

  • Wang YY, Khoo KH, Chen ST, Lin CC, Wong CH, Lin CH (2002) Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activites. Bioorg Med Chem 10:1057–1062

    Article  CAS  Google Scholar 

  • Ward C, Chilvers ED, Lawson MF, Pryde JG, Fujihara S, Farrow SN, Haslett C, Rossi AG (1999) NF-κB activation is a critical regulator of human granulocyte apoptosis in vitro. J Biol Chem 274:4309–4318

    Article  CAS  Google Scholar 

  • Waring P, Beaver J (1996) Gliotoxin and related epipolythiodioxopiperazines. Gen Pharmacol 27:1311–1316

    Article  CAS  Google Scholar 

  • Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60:258–274

    Article  CAS  Google Scholar 

  • Wasser SP, Weis AL (1999) Medicinal properties of substances occurring in higher basidiomycetes mushrooms: current perspectives. Int J Med Mushrooms 1:31–62

    Article  CAS  Google Scholar 

  • Wasser SP, Elisashivili VI, Tan KK (2003) Effects of carbon and nitrogen sources in the medium on Tremella mesenterica Retz.: Fr. (Heterobasidiomycetes) growth and polysaccharide production. Int J Med Mushrooms 5:49–56

    Article  CAS  Google Scholar 

  • Weber G, Leitner E (1994) Disruption of the cyclosporine synthetase gene of Tolypocladium niveum. Curr Gent 26:461–467

    Article  CAS  Google Scholar 

  • Weber G, Schörgendorfer K, Schneider-Scherzer E, Leitner E (1994) The peptide synthetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 458-kilobase open reading frame. Curr Genet 26:120–125

    Article  CAS  Google Scholar 

  • Xu ZN, Yang S-T (2007) Production of mycophenolic acid by Penicillium brevicompactum immobilized in a rotating fibrous-bed bioreactor. Enz Microb Technol 40:623–628

    Article  CAS  Google Scholar 

  • Yalin W, Ishurd O, Cuirong S, Yuanjiang P (2005) Structure analysis and anti-tumor activity of (1→3)-β-D-glucans (cordyglucans) from the mycelia of Cordyceps sinensis. Planta Medica 71:381–384

    Article  CAS  Google Scholar 

  • Yamada A, Kataoka T, Nagai K (2000) The fungal metabolite gliotoxin: immunosuppressive activity on CTL-mediated cytotoxicity. Immunol Lett 71:27–32

    Article  CAS  Google Scholar 

  • Yang B-K, Gu Y-A, Jeong Y-T, Jeong H, Song C-H (2007) Chemical characteristics and immune-modulating activities of exo-biopolymers produced by Grifola frondosa during submerged fermentation process. Int J Biol Macromol 41:327–333

    Article  CAS  Google Scholar 

  • Yang L, Wang R, Liu J, Tong H, Deng Y, Li Q (2004) The effect of polyporus umbellatus polysaccharide on the immunosuppression property of culture supernatant of S180 cells. Chin J Cell Mol Immunol 20:234–237

    CAS  Google Scholar 

  • Yonezawa S, Komurasaki T, Kawada K, Tsuri T, Fuji M, Kugimiya A, Haga N, Mitsumori S, Inagaki M, Nakatani T, Tamura Y, Takechi S, Taishi T, Ohtani M (1998) Total synthesis of terprenin, a novel immunosuppressive p-terphenyl derivative. J Org Chem 63:5831–5837

    Article  CAS  Google Scholar 

  • Zhang M, Cui SW, Cheung PCK, Wang Q (2007) Antitumor polysaccharides from mushrooms: a review on their isolation process, structural characteristics and antitumor activity. Trends Food Sci Technol 18:4–19

    Article  CAS  Google Scholar 

  • Zhang P, Cheung PCK (2002) Evaluation of sulfated Lentinus edodes α-(1→3)-D-glucan as a potential antitumor agent. Biosci Biotechnol Biochem 66:1052–1056

    Article  CAS  Google Scholar 

  • Zhang WY, Wang Y, Hou YY (2004) Effects of Chinese medicinal fungus water extract on tumor metastasis and some parameters of immune function. Int Immunopharmacol 4:461–468

    Article  CAS  Google Scholar 

  • Zhong JJ, Tang YJ (2004) Submerged cultivation of medicinal mushrooms for production of valuable bioactive metabolites. Adv Biochem Eng Biotechnol 87:25–59

    CAS  Google Scholar 

  • Zou X (2006) Fed-batch fermentation for hyperproduction of polysaccharide and ergosterol by medicinal mushroom Agaricus brasiliensis. Process Biochem 41:970–974

    Article  CAS  Google Scholar 

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  1. Chemical Engineering Pilot Plant (CEPP), Faculty of Chemical and Natural Resources Engineering, Universiti Teknologi Malaysia (UTM), 81310, Skudai, Johor, Malaysia

    Hesham El Enshasy

  2. Bioprocess Development Department, Mubarak City for Scientific Research and Technology Applications (MuCSAT), New Burg Al Arab, Alexandria, Egypt

    Hesham El Enshasy

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  1. , Department of Biotechnology, International Graduate School of Zittau, Markt 23, Zittau, 02763, Sachsen, Germany

    Martin Hofrichter

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Enshasy, H.E. (2011). Immunomodulators. In: Hofrichter, M. (eds) Industrial Applications. The Mycota, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11458-8_8

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