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Secondary Metabolite Production by Endophytic Fungi: The Gene Clusters, Nature, and Expression

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Endophytes and Secondary Metabolites

Part of the book series: Reference Series in Phytochemistry ((RSP))

Abstract

With the recent advancements in drug discovery, the bioprospecting of endophytic fungi for the search of secondary metabolites of pharmaceutical importance and novel medicinal properties has become one of the prime targets. The biosynthetic pathways that are responsible for secondary metabolites have genetic basis for their production. But the expression of the gene clusters responsible for secondary metabolites remains cryptic under laboratory conditions. The large-scale production of these metabolites is severely distressed by its attenuation in axenic cultures. Our insights into these clusters, their regulation, and expression may lead to the mining of more novel bioactive metabolites. This approach of genome mining for the production of novel metabolites is assuring. Major challenges lie in the understanding of the regulatory mechanisms which drive the expression of these cryptic genes. Gaining knowledge on various strategies for the identification as well as induction of these silent clusters is the need of the hour. With the help of multidisciplinary scientific approaches involving bioinformatics, molecular genetics, genome mining, metabolomics, etc., we can explore the hidden treasures of the endophytic fungal diversity.

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Abbreviations

BGCs:

Biosynthetic gene clusters

SMs:

Secondary metabolites

References

  1. Nathan C, Cars O (2014) Antibiotic resistance – problems, progress, and prospects. N Engl J Med 371:1761–1763

    Article  PubMed  Google Scholar 

  2. Brakhage AA (2013) Regulation of fungal secondary metabolism. Nat Rev Microbiol 11:21

    Article  CAS  PubMed  Google Scholar 

  3. Martins A, Vieira H, Gaspar H, Santos S (2014) Marketed marine natural products in the pharmaceutical and cosmeceutical industries: Tips for success. Mar Drugs 12:1066–1101

    Article  PubMed  PubMed Central  Google Scholar 

  4. Berdy J (2005) Bioactive microbial metabolites. J Antibiot (Tokyo) 58:1

    Article  CAS  Google Scholar 

  5. Petrini O (1991) Fungal endophytes of tree leaves. In: Microbial ecology of leaves. Springer, New York, pp 179–197

    Chapter  Google Scholar 

  6. Carroll GC (1986) The biology of endophytism in plants with particular reference to woody perennials. In: Microbiology of Phyllosphere. Cambridge University Press, London, pp 203–222

    Google Scholar 

  7. Krings M, Taylor TN, Hass H, Kerp H, Dotzler N, Hermsen EJ (2007) Fungal endophytes in a 400-million-yr-old land plant: infection pathways, spatial distribution, and host responses. New Phytol 174:648–657

    Article  PubMed  Google Scholar 

  8. Sun X, Guo L-D (2012) Endophytic fungal diversity: review of traditional and molecular techniques. Mycology 3:65–76

    Google Scholar 

  9. Rodriguez RJ, White Jr JF, Arnold AE, Redman RS (2009) Fungal endophytes: diversity and functional roles. New Phytol 182:314–330

    Article  CAS  PubMed  Google Scholar 

  10. Sun X, Guo L-D, Hyde KD (2011) Community composition of endophytic fungi in Acer truncatum and their role in decomposition. Fungal Divers 47:85–95

    Article  Google Scholar 

  11. Mishra R, Sarma VV (2017) Mycoremediation of heavy metal and hydrocarbon pollutants by endophytic Fungi. In: Mycoremediation and environmental sustainability. Springer, pp 133–151

    Google Scholar 

  12. Yim G, Wang HH (2007) Antibiotics as signalling molecules. Philos Trans R Soc B Biol Sci 362:1195–1200

    Article  CAS  Google Scholar 

  13. Gouda S, Das G, Sen SK, Shin H-S, Patra JK (2016) Endophytes: a treasure house of bioactive compounds of medicinal importance. Front Microbiol 7:1538

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ludwig-Müller J (2015) Plants and endophytes: equal partners in secondary metabolite production? Biotechnol Lett 37:1325–1334

    Article  PubMed  CAS  Google Scholar 

  15. Rohlfs M, Albert M, Keller NP, Kempken F (2007) Secondary chemicals protect mould from fungivory. Biol Lett 3:523–525

    Article  PubMed  PubMed Central  Google Scholar 

  16. Nicoletti R, Fiorentino A (2015) Plant bioactive metabolites and drugs produced by endophytic fungi of Spermatophyta. Agriculture 5:918–970

    Article  CAS  Google Scholar 

  17. Stierle AA, Stierle DB (2015) Bioactive secondary metabolites produced by the fungal endophytes of conifers. Nat Prod Commun 10:1671

    PubMed  PubMed Central  Google Scholar 

  18. Schulz B, Boyle C, Draeger S, Römmert A-K, Krohn K (2002) Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol Res 106:996–1004

    Article  CAS  Google Scholar 

  19. Martinez-Klimova E, Rodríguez-Peña K, Sánchez S (2017) Endophytes as sources of antibiotics. Biochem Pharmacol 134:1–17

    Article  CAS  PubMed  Google Scholar 

  20. Mishra R, Meena H, Meena C, Kushveer JS, Busi S, Murali A, Sarma VV (2018) Anti-quorum sensing and antibiofilm potential of Alternaria alternata, a foliar endophyte of Carica papaya, evidenced by QS assays and in-silico analysis. Fungal Biol. https://doi.org/10.1016/j.funbio.2018.07.003.

    Article  CAS  PubMed  Google Scholar 

  21. Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism – from biochemistry to genomics. Nat Rev Microbiol 3:937

    Article  CAS  PubMed  Google Scholar 

  22. Brakhage AA, Bergmann S, Schuemann J, Scherlach K, Schroeckh V, Hertweck C (2009) Fungal genome mining and activation of silent gene clusters. In: Physiology and genetics. Springer, Berlin, Heidelberg. pp 297–303

    Chapter  Google Scholar 

  23. Brakhage AA, Schroeckh V (2011) Fungal secondary metabolites–strategies to activate silent gene clusters. Fungal Genet Biol 48:15–22

    Article  CAS  PubMed  Google Scholar 

  24. Netzker T, Fischer J, Weber J, Mattern DJ, König CC, Valiante V, Schroeckh V, Brakhage AA (2015) Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front Microbiol 6:299

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wiemann P, Keller NP (2014) Strategies for mining fungal natural products. J Ind Microbiol Biotechnol 41:301–313

    Article  CAS  PubMed  Google Scholar 

  26. Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, Weber T, Takano E, Breitling R (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cimermancic P, Medema MH, Claesen J, Kurita K, Brown LCW, Mavrommatis K, Pati A, Godfrey PA, Koehrsen M, Clardy J (2014) Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 158:412–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. MacCabe AP, Riach MB, Unkles SE, Kinghorn JR (1990) The Aspergillus nidulans npeA locus consists of three contiguous genes required for penicillin biosynthesis. EMBO J 9:279–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Smith DJ, Burnham MKR, Edwards J, Earl AJ, Turner G (1990) Cloning and heterologous expression of the penicillin biosynthetic gene cluster from Penicillium chrysogenum. Nat Biotechnol 8:39

    Article  CAS  Google Scholar 

  30. Kimura M, Tokai T, Takahashi-Ando N, Ohsato S, Fujimura M (2007) Molecular and genetic studies of Fusarium trichothecene biosynthesis: pathways, genes, and evolution. Biosci Biotechnol Biochem 71:2105–2123

    Article  CAS  PubMed  Google Scholar 

  31. Wisecaver JH, Rokas A (2015) Fungal metabolic gene clusters – caravans traveling across genomes and environments. Front Microbiol 6:161

    Article  PubMed  PubMed Central  Google Scholar 

  32. Smith DJ, Burnham MK, Bull JH, Hodgson JE, Ward JM, Browne P, Brown J, Barton B, Earl AJ, Turner G (1990) Beta-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes. EMBO J 9:741–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Deepika VB, Murali TS, Satyamoorthy K (2016) Modulation of genetic clusters for synthesis of bioactive molecules in fungal endophytes: a review. Microbiol Res 182:125–140

    Article  CAS  PubMed  Google Scholar 

  34. Nei M (2003) Genome evolution: let’s stick together. Heredity (Edinb) 90:411

    Article  CAS  Google Scholar 

  35. Medema MH, Van Raaphorst R, Takano E, Breitling R (2012) Computational tools for the synthetic design of biochemical pathways. Nat Rev Microbiol 10:191

    Article  CAS  PubMed  Google Scholar 

  36. Nielsen JC, Nielsen J (2017) Development of fungal cell factories for the production of secondary metabolites: linking genomics and metabolism. Synth Syst Biotechnol 2:5–12

    Article  PubMed  PubMed Central  Google Scholar 

  37. Gao X, Chooi Y-H, Ames BD, Wang P, Walsh CT, Tang Y (2011) Fungal indole alkaloid biosynthesis: genetic and biochemical investigation of the tryptoquialanine pathway in Penicillium aethiopicum. J Am Chem Soc 133:2729–2741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chooi Y-H, Cacho R, Tang Y (2010) Identification of the viridicatumtoxin and griseofulvin gene clusters from Penicillium aethiopicum. Chem Biol 17:483–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yeh H-H, Ahuja M, Chiang Y-M, Oakley CE, Moore S, Yoon O, Hajovsky H, Bok J-W, Keller NP, Wang CCC (2016) Resistance gene-guided genome mining: serial promoter exchanges in Aspergillus nidulans reveal the biosynthetic pathway for fellutamide B, a proteasome inhibitor. ACS Chem Biol 11:2275–2284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tang X, Li J, Millán-Aguiñaga N, Zhang JJ, O’Neill EC, Ugalde JA, Jensen PR, Mantovani SM, Moore BS (2015) Identification of thiotetronic acid antibiotic biosynthetic pathways by target-directed genome mining. ACS Chem Biol 10:2841–2849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bergmann S, Schümann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3:nchembio869

    Article  CAS  Google Scholar 

  42. Chiang Y-M, Chang S-L, Oakley BR, Wang CCC (2011) Recent advances in awakening silent biosynthetic gene clusters and linking orphan clusters to natural products in microorganisms. Curr Opin Chem Biol 15:137–143

    Article  CAS  PubMed  Google Scholar 

  43. Bertrand S, Schumpp O, Bohni N, Bujard A, Azzollini A, Monod M, Gindro K, Wolfender J-L (2013) Detection of metabolite induction in fungal co-cultures on solid media by high-throughput differential ultra-high pressure liquid chromatography–time-of-flight mass spectrometry fingerprinting. J Chromatogr A 1292:219–228

    Article  CAS  PubMed  Google Scholar 

  44. Estrada AER, Hegeman A, Kistler HC, May G (2011) In vitro interactions between Fusarium verticillioides and Ustilago maydis through real-time PCR and metabolic profiling. Fungal Genet Biol 48:874–885

    Article  CAS  Google Scholar 

  45. Schroeckh V, Scherlach K, Nützmann H-W, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009) Intimate bacterial–fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci 106:14558–14563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mela F, Fritsche K, De Boer W, Van Veen JA, De Graaff LH, Van Den Berg M, Leveau JHJ (2011) Dual transcriptional profiling of a bacterial/fungal confrontation: Collimonas fungivorans versus Aspergillus niger. ISME J 5:1494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fischer J, Schroeckh V, Brakhage AA (2016) Awakening of fungal secondary metabolite gene clusters. In: Gene expression systems in fungi: advancements and applications. Springer, Cham, pp 253–273

    Chapter  Google Scholar 

  48. Rateb ME, Hallyburton I, Houssen WE, Bull AT, Goodfellow M, Santhanam R, Jaspars M, Ebel R (2013) Induction of diverse secondary metabolites in Aspergillus fumigatus by microbial co-culture. RSC Adv 3:14444–14450

    Article  CAS  Google Scholar 

  49. Li C, Wang J, Luo C, Ding W, Cox DG (2014) A new cyclopeptide with antifungal activity from the co-culture broth of two marine mangrove fungi. Nat Prod Res 28:616–621

    Article  CAS  PubMed  Google Scholar 

  50. Chiang Y-M, Lee K-H, Sanchez JF, Keller NP, Wang CCC (2009) Unlocking fungal cryptic natural products. Nat Prod Commun 4:1505

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Bode HB, Bethe B, Höfs R, Zeeck A (2002) Big effects from small changes: possible ways to explore nature’s chemical diversity. Chembiochem 3:619–627

    Article  CAS  PubMed  Google Scholar 

  52. Lin Z, Zhu T, Wei H, Zhang G, Wang H, Gu Q (2009) Spicochalasin A and new Aspochalasins from the marine-derived fungus Spicaria elegans. Eur J Org Chem 2009:3045–3051

    Article  CAS  Google Scholar 

  53. Andersen MR, Nielsen JB, Klitgaard A, Petersen LM, Zachariasen M, Hansen TJ, Blicher LH, Gotfredsen CH, Larsen TO, Nielsen KF (2013) Accurate prediction of secondary metabolite gene clusters in filamentous fungi. Proc Natl Acad Sci 110:E99–E107

    Article  CAS  PubMed  Google Scholar 

  54. Gerke J, Bayram Ö, Feussner K, Landesfeind M, Shelest E, Feussner I, Braus GH (2012) Breaking the silence: protein stabilization uncovers silenced biosynthetic gene clusters in the fungus Aspergillus nidulans. Appl Environ Microbiol 78:8234–8244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kennedy J, Turner G (1996) δ-(l-α-Aminoadipyl)-l-cysteinyl-d-valine synthetase is a rate limiting enzyme for penicillin production in Aspergillus nidulans. Mol Gen Genet MGG 253:189–197

    Article  CAS  PubMed  Google Scholar 

  56. Sanchez JF, Somoza AD, Keller NP, Wang CCC (2012) Advances in Aspergillus secondary metabolite research in the post-genomic era. Nat Prod Rep 29:351–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gacek A, Strauss J (2012) The chromatin code of fungal secondary metabolite gene clusters. Appl Microbiol Biotechnol 95:1389–1404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bulger M (2005) Hyperacetylated chromatin domains: lessons from heterochromatin. J Biol Chem 280:21689–21692

    Article  CAS  PubMed  Google Scholar 

  59. Lee I, Oh J-H, Shwab EK, Dagenais TRT, Andes D, Keller NP (2009) HdaA, a class 2 histone deacetylase of Aspergillus fumigatus, affects germination and secondary metabolite production. Fungal Genet Biol 46:782–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Shwab EK, Bok JW, Tribus M, Galehr J, Graessle S, Keller NP (2007) Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot Cell 6:1656–1664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Williams RB, Henrikson JC, Hoover AR, Lee AE, Cichewicz RH (2008) Epigenetic remodeling of the fungal secondary metabolome. Org Biomol Chem 6:1895–1897

    Article  CAS  PubMed  Google Scholar 

  62. Ola ARB, Thomy D, Lai D, Brötz-Oesterhelt H, Proksch P (2013) Inducing secondary metabolite production by the endophytic fungus Fusarium tricinctum through coculture with Bacillus subtilis. J Nat Prod 76:2094–2099

    Article  CAS  PubMed  Google Scholar 

  63. Mao X, Xu W, Li D, Yin W, Chooi Y, Li Y, Tang Y, Hu Y (2015) Epigenetic genome mining of an endophytic fungus leads to the pleiotropic biosynthesis of natural products. Angew Chemie Int Ed 54:7592–7596

    Article  CAS  Google Scholar 

  64. Sharma VK, Kumar J, Singh DK, Mishra A, Verma SK, Gond SK, Kumar A, Singh N, Kharwar RN (2017) Induction of cryptic and bioactive metabolites through natural dietary components in an endophytic fungus Colletotrichum gloeosporioides (Penz.) Sacc. Front Microbiol 8:1126

    Article  PubMed  PubMed Central  Google Scholar 

  65. Li YF, Tsai KJS, Harvey CJB, Li JJ, Ary BE, Berlew EE, Boehman BL, Findley DM, Friant AG, Gardner CA (2016) Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products. Fungal Genet Biol 89:18–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Schmitt EK, Hoff B, Kück U (2004) AcFKH1, a novel member of the forkhead family, associates with the RFX transcription factor CPCR1 in the cephalosporin C-producing fungus Acremonium chrysogenum. Gene 342:269–281

    Article  CAS  PubMed  Google Scholar 

  67. Ichikawa N, Sasagawa M, Yamamoto M, Komaki H, Yoshida Y, Yamazaki S, Fujita N (2012) DoBISCUIT: a database of secondary metabolite biosynthetic gene clusters. Nucleic Acids Res 41:D408–D414

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Umemura M, Koike H, Nagano N, Ishii T, Kawano J, Yamane N, Kozone I, Horimoto K, Shin-ya K, Asai K (2013) MIDDAS-M: motif-independent de novo detection of secondary metabolite gene clusters through the integration of genome sequencing and transcriptome data. PLoS One 8:e84028

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Khaldi N, Seifuddin FT, Turner G, Haft D, Nierman WC, Wolfe KH, Fedorova ND (2010) SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol 47:736–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bumpus SB, Evans BS, Thomas PM, Ntai I, Kelleher NL (2009) A proteomics approach to discovering natural products and their biosynthetic pathways. Nat Biotechnol 27:951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gogarten JP, Townsend JP (2005) Horizontal gene transfer, genome innovation and evolution. Nat Rev Microbiol 3:679

    Article  CAS  PubMed  Google Scholar 

  72. Campbell MA, Rokas A, Slot JC (2012) Horizontal transfer and death of a fungal secondary metabolic gene cluster. Genome Biol Evol 4:289–293

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Lim FY, Sanchez JF, Wang CCC, Keller NP (2012) Toward awakening cryptic secondary metabolite gene clusters in filamentous fungi. In: Methods in enzymology. Elsevier, Amsterdam, pp 303–324

    Google Scholar 

  74. Knox BP, Keller NP (2015) Key players in the regulation of fungal secondary metabolism. In: Biosynthesis and molecular genetics of fungal secondary metabolites, vol 2. Springer, New York, NY, pp 13–28

    Google Scholar 

  75. Chang P-K, Yu J, Bhatnagar D, Cleveland TE (2000) Characterization of the Aspergillus parasiticus major nitrogen regulatory gene, areA. Biochim Biophys Acta (BBA)-Gene Struct Expr 1491:263–266

    Article  CAS  Google Scholar 

  76. Trushina N, Levin M, Mukherjee PK, Horwitz BA (2013) PacC and pH–dependent transcriptome of the mycotrophic fungus Trichoderma virens. BMC Genomics 14:138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Schmitt E, Kempken R, Kück U (2001) Functional analysis of promoter sequences of cephalosporin C biosynthesis genes from Acremonium chrysogenum: specific DNA-protein interactions and characterization of the transcription factor PACC. Mol Gen Genomics 265:508–518

    Article  CAS  Google Scholar 

  78. Ronne H (1995) Glucose repression in fungi. Trends Genet 11:12–17

    Article  CAS  PubMed  Google Scholar 

  79. Jekosch K, Kück U (2000) Glucose dependent transcriptional expression of the cre1 gene in Acremonium chrysogenum strains showing different levels of cephalosporin C production. Curr Genet 37:388–395

    Article  CAS  PubMed  Google Scholar 

  80. Bayram Ö, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O, Braus-Stromeyer S, Kwon N-J, Keller NP, Yu J-H (2008) VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science (80-) 320:1504–1506

    Article  CAS  Google Scholar 

  81. Duran RM, Cary JW, Calvo AM (2007) Production of cyclopiazonic acid, aflatrem, and aflatoxin by Aspergillus flavus is regulated by veA, a gene necessary for sclerotial formation. Appl Microbiol Biotechnol 73:1158

    Article  CAS  PubMed  Google Scholar 

  82. Hortschansky P, Eisendle M, Al-Abdallah Q, Schmidt AD, Bergmann S, Thön M, Kniemeyer O, Abt B, Seeber B, Werner ER (2007) Interaction of HapX with the CCAAT-binding complex – a novel mechanism of gene regulation by iron. EMBO J 26:3157–3168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chang P-K, Ehrlich KC, Yu J, Bhatnagar D, Cleveland TE (1995) Increased expression of Aspergillus parasiticus aflR, encoding a sequence-specific DNA-binding protein, relieves nitrate inhibition of aflatoxin biosynthesis. Appl Environ Microbiol 61:2372–2377

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Yu J-H, Butchko RAE, Fernandes M, Keller NP, Leonard TJ, Adams TH (1996) Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus. Curr Genet 29:549–555

    Article  CAS  PubMed  Google Scholar 

  85. Woloshuk CP, Foutz KR, Brewer JF, Bhatnagar D, Cleveland TE, Payne GA (1994) Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis. Appl Environ Microbiol 60:2408–2414

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Fernandes M, Keller NP, Adams TH (1998) Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol Microbiol 28:1355–1365

    Article  CAS  PubMed  Google Scholar 

  87. Hong S-Y, Roze LV, Linz JE (2013) Oxidative stress-related transcription factors in the regulation of secondary metabolism. Toxins (Basel) 5:683–702

    Article  CAS  Google Scholar 

  88. Roze LV, Chanda A, Wee J, Awad D, Linz JE (2011) Stress-related transcription factor AtfB integrates secondary metabolism with oxidative stress response in aspergilli. J Biol Chem 286:35137–35148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Reverberi M, Gazzetti K, Punelli F, Scarpari M, Zjalic S, Ricelli A, Fabbri AA, Fanelli C (2012) Aoyap1 regulates OTA synthesis by controlling cell redox balance in Aspergillus ochraceus. Appl Microbiol Biotechnol 95:1293–1304

    Article  CAS  PubMed  Google Scholar 

  90. Yin W, Amaike S, Wohlbach DJ, Gasch AP, Chiang Y, Wang CCC, Bok JW, Rohlfs M, Keller NP (2012) An Aspergillus nidulans bZIP response pathway hardwired for defensive secondary metabolism operates through aflR. Mol Microbiol 83:1024–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Sciences, Pondicherry University, Puducherry, India

    Mishra Rashmi & V. Venkateswara Sarma

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  1. Mishra Rashmi
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Correspondence to V. Venkateswara Sarma .

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  1. Department of Botany, University of Calcutta, Kolkata, West Bengal, India

    Sumita Jha

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Rashmi, M., Venkateswara Sarma, V. (2019). Secondary Metabolite Production by Endophytic Fungi: The Gene Clusters, Nature, and Expression. In: Jha, S. (eds) Endophytes and Secondary Metabolites. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-90484-9_20

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