Antibiotics pp 97-146 | Cite as

Strain Improvement and Preservation of β-Lactam-Producing Microorganisms

  • R. P. Elander
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 67 / 1)

Abstract

The initial discovery of Fleming’s contaminating Penicillium fungus and its remarkable antibacterial properties now date back more than 50 years. Although the Oxford group proposed in 1943 that penicillin contained a fused β-lactam ring, its structure was not generally accepted until it was confirmed by x-ray crystallographic studies of Hokgkin and Low in 1945 (Crowfoot et al. 1949; Abraham 1978). The reactivity of the β-lactam ring is undoubtedly one of the major factors for its intrinsic antibacterial activity.

Keywords

Valine Peptone Thiosulfate Scenedesmus Penicillamine 

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References

  1. Abraham EP (1978) Developments in the chemistry and biochemistry of β-lactam antibiotics. In: Hütter R, Leisinger T, Nüesch J, Wehrli W (eds) Antibiotics and other secondary metabolites. Academic Press, New York, pp 141–164Google Scholar
  2. Abraham EP (1979) A glimpse of the early history of cephalosporins. Rev Infect Dis 1:99–105PubMedGoogle Scholar
  3. Abraham EP, Newton GGF, Hale CW (1954) Purification and some properties of cephalosporin N, a new penicillin. Biochem J 58:94–102PubMedGoogle Scholar
  4. Aoki H, Okuhara M (1980) Natural β-lactam antibiotics. Ann Rev Microbiol 34:159–181Google Scholar
  5. Aoki H, Sakai H, Kohsaka M, Konomi T, Hosoda J, Kubochi Y, Iguchi E, Imanaka H (1976) Nocardicin, a new β-lactam antibiotic. I. Discovery, isolation and characterization. J Antibiot 29:492–500PubMedGoogle Scholar
  6. Aoki H, Kunugita K, Hosoda J, Imanaka H (1977) Screening of new and novel β–lactam antibiotics. J Antibiot [Suppl] 30:S–207–2–217Google Scholar
  7. Arnstein HRV, Morris D (1960) The structure of a peptide containing a-aminoadipic acid, cysteine, and valine, present in the mycelium of Penicillium chrysogenum. Biochem J 76:357–366PubMedGoogle Scholar
  8. Backus MP, Stauffer JF (1955) The production and selection of a family of strains in Penicillium chrysogenum. Mycologia 47:429–463Google Scholar
  9. Ball C, McGonagle MP (1978) Development and evaluation of a potency index screen for detecting mutants of Penicillium chrysogenum having increased penicillin yield. J Appl Bacteriol 45:67–74PubMedGoogle Scholar
  10. Batchelor FR, Doyle FP, Nayler THC, Rolinson GN (1959) Synthesis of penicillin 6-aminopenicillanic acid in penicillin fermentations. Nature 183:257–258PubMedGoogle Scholar
  11. Behrens OK (1949) Biosynthesis of penicillin: In: Clarke HT, Johnson TR, Robinson R (eds) The chemistry of penicillin. Princeton University Press, Princeton, pp 657–679Google Scholar
  12. Box SJ, Hood JD, Sear S (1979) Four further antibiotics related to olivanic acid produced by Streptomyces olivaceus. Fermentation, isolation, characterization, and biosynthesis studies. J Antibiot 32:1239–1247PubMedGoogle Scholar
  13. Brannon DR, Fukuda DS, Mabe JA, Huber FM, Whitney JG (1972) Detection of a cephalosporin C acetyl esterase in the carbamate cephalosporin antibiotic producing culture, Streptomyces clavuligerus. Antimicrob Agents Chemother 1:237–241PubMedGoogle Scholar
  14. Brown AG, Butterworth D, Cole M, Hanscomb G, Hood JD, Reading C, Rolinson GN (1976) Naturally occuring β-lactamase inhibitors with antibacterial activity. J Antibiot 29:668–669PubMedGoogle Scholar
  15. Brown AG, Corbett DF, Englington AJ, Howarth TT (1977) Structures of olivanic acid derivatives MM4550 and MMI3902, two new fused β-lactams isolated from Streptomyces olivaceus. J Chem Soc [D] 1977:523–525Google Scholar
  16. Brown WF, Elander RP (1966) Some biometric considerations in an applied antibiotic AB-464 strain development program. Dev Ind Microbiol 7:114–123Google Scholar
  17. Burton HS, Abraham EP (1951) Isolation of antibiotics from a species of Cephalosporium: P1, P2, P3, P4, and P5. Biochem J 50:168–174PubMedGoogle Scholar
  18. Butterworth D, Cole M, Hanscomb G, Rolinson GN (1979) Olivanic acids, a family of βlactam antibiotics with β-lactamase inhibitory properties produced by a Streptomyces species. I. Detection, properties, and fermentation studies. J Antibiot 32:287–294PubMedGoogle Scholar
  19. Cassidy PJ (1981) Novel naturally occurring β-lactam antiobitics - a review. Dev Ind Microbiol 22:181–209Google Scholar
  20. Chang LT, Elander RP (1979) Rational selection for improved productivity in strains of Acremonium chrysogenum Gams. Dev Ind Microbiol 20:367–379Google Scholar
  21. Cole M (1979) Inhibition of β-lactamases. In: Hamilton-Miller JMT, Smith JT (eds) BetaLactamases. Academic Press, New York, pp 205–289Google Scholar
  22. Cole M, Batchelor FR (1963) Aminoadipylpenicillin in penicillin fermentations. Nature 198:383–384PubMedGoogle Scholar
  23. Cole M, Rolinson GN (1961) 6-Aminopenicillanic acid II. Formation of 6-aminopenicillanic acid by Emericellopsis minima (Stolk) and related fungi. Proc R Soc Lond [Biol] 154:490–497Google Scholar
  24. Cole M, Howarth TT, Reading C (1976) Ger Offen 2:517, 316Google Scholar
  25. Cooney CL (1979) Conversion yields in penicillin production: theory vs. practice. Proc Biochem 14:31–33Google Scholar
  26. Crawford K, Heatley NG, Boyd PF, Hale CW, Kelley BK, Miller GA, Smith N (1952) Antibiotic production by a species of Cephalosporium. J Gen Microbiol 6:41–59Google Scholar
  27. Crawfoot D, Bunn CW, Rogers-Low BW, Turner-Jones A (1949) The x-ray crystallographic investigation of the structure of penicillin. In: Clarke HT, Johnson JR, Robinson R (eds) The chemistry of penicillin. Princeton University Press, Princeton, pp 310–366Google Scholar
  28. Daily WA, Higgens CE (1973) Preservation and storage of microorganisms in the gas phase of liquid nitrogen. Cryobiology 10:364–367PubMedGoogle Scholar
  29. Demain AL, Masurekar PS (1974) Lysine inhibition of in vivo homocitrate synthesis in Penicillium chrysogenum. J Gen Microbiol 82:143–151PubMedGoogle Scholar
  30. Demain AL, Newkirk JF, Davis GE, Harman RE (1963) Nonbiological conversion of cephalosporin C to a new antibiotic by sodium thiosulfate. Appl Microbiol 11:58–61PubMedGoogle Scholar
  31. Dennen DW, Carver DD (1969) Sulfatase regulation and antibiotic synthesis in Cephalosporium acremonium. Can J Microbiol 15:175–181PubMedGoogle Scholar
  32. Doudoroff M, Palleroni NJ (1974) Part 7. Gram-negative aerobic rods and cocci. In: Buchanan RE, Gibbons NE (eds) Bergey’s manual of determinative bacteriology, 8th ed. Williams & Wilkens, Baltimore, pp 217–243Google Scholar
  33. Drew SW, Demain AL (1977) Effect of primary metabolites on secondary metabolism. Ann Rev Microbiol 31:343–356Google Scholar
  34. Drew SW, Winstanley DJ, Demain AL (1976) Effect of norleucine on morphological differentiation in Cephalosporium acremonium. Appl Microbiol 31:143–145Google Scholar
  35. Dulaney EL (1947) Some aspects of penicillin production by Aspergillus nidulans. Mycologia 39:570–582PubMedGoogle Scholar
  36. Dulaney EL, Dulaney DD (1967) Mutant populations of Streptomyces viridifaciens. Trans NY Acad Sci 29:782–799Google Scholar
  37. Elander RP (1967) Enhanced penicillin biosynthesis in mutant and recombinant strains of Penicillium chrysogenum. In: Stübbe H (ed) Induced mutations and their utilization. Academie-Verlag, Berlin, pp 403–423Google Scholar
  38. Elander RP (1975) Genetic aspects of cephalosporin and cephamycin-producing microorganisms. Dev Ind Microbiol 16:356–374Google Scholar
  39. Elander RP (1976) Mutation to increased product formation in antibiotic producing microorganisms. In: Schlessinger D (ed) Microbiology-1976. American Society of Microbiology, Washington, D.C., pp 517–521Google Scholar
  40. Elander RP (1978) Maintenance and productivity of industrially important fungi (Abstr). XII International Congress of Microbiology, Munich, No. S28.1, p 39Google Scholar
  41. Elander RP (1979) Mutations affecting antibiotic synthesis in fungi producing β-lactam antibiotics. In: Sebek OK, Laskin AI (eds) Genetics of industrial microorganisms. American Society of Microbiology, Washington, D.C., pp 21–35Google Scholar
  42. Elander RP, Aoki H (1982) β-Lactam producing microorganisms - their biology and fermentation behavior. In: Morin RB, Gorman M (eds) Chemistry and biology of β-lactam antibiotics, vol 3. Academic Press, New York, pp 83–153Google Scholar
  43. Elander RP, Chang LT (1979) Microbial culture selection. In: Peppler H, Perlman D (eds) Microbiology technology, 2nd edn, vol 2. Academic Press, New York, pp 243–302Google Scholar
  44. Elander RP, Stauffer JF, Backus MP (1961) Antibiotic production by various species and varities of Cephalosporium and Emericellopsis. Antimicrob Agents Ann 1:91–102Google Scholar
  45. Elander RP, Gordee RS, Wilgus RM, Gale RM (1969) Synthesis of an antibiotic closely resembling fusidic acid by imperfect and perfect dermatophyte fungi. J Antibiot 22:176178Google Scholar
  46. Elander RP, Espenshade MA, Pathak SG, Pan CH (1973) The use of parasexual genetics in an industrial strain improvement program with Penicillium chrysogenum. In: Vanek Z, Hostalek Z, Cudlin J (eds) Genetics of industrial microorganisms, vol 2. Actinomycetes and fungi. Elsevier, Amsterdam, pp 239–253Google Scholar
  47. Elander RP, Corum CJ, DeValeria H, Wilgus RM (1976) Ultraviolet mutagenesis and cephalosporin synthesis in strains of Cephalosporium acremonium. In: Macdonald KD (ed) Second international symposium on the genetics of industrial microorganisms. Academic Press, London, pp 253–271Google Scholar
  48. Erickson RC, Dean LD (1966) Acylation of 6-aminopenicillanic acid by Penicillium chrysogenum. Appl Microbiol 14:1047–1048PubMedGoogle Scholar
  49. Fasani M, Marini F, Teatini L (1974) Variability of cephalosporin C production induced by phenethyl alcohol and dimethylsulfate (Astr). Second international symposium on genetics of industrial microorganisms. Academic Press, London, p 31Google Scholar
  50. Fleischman HI, Pisano MA (1961) The production of synnematin B by Paecilomyces persicinus in a chemically defined medium. Antimicrob Agents Ann 1:48–53Google Scholar
  51. Fleming A (1929) On the antibacterial action of cultures of a penicillin, with special reference to their use in the isolation of B. influenzae. Br J Exp Pathol 10:226–236Google Scholar
  52. Florey HW, Chain EB, Heatley NG, Jennings MA, Sanders AG, Abraham EP, Florey ME (eds) (1949) Antibiotics, vol 2. Oxford University Press, London New YorkGoogle Scholar
  53. Flynn EH, McCormick MH, Stamper MC, DeValeria H, Godzeski CW (1962) A new natural penicillin from Penicillium chrysogenum. J Am Chem Soc 84:4594–4595Google Scholar
  54. Fortney KF, Thoma RW (1977) Stabilization of culture productivity. Dev Ind Microbiol 18:319–325Google Scholar
  55. Friedrich CG, Demain AL (1977 a) Homocitrate synthase as the crucial site of the lysine effect on penicillin biosynthesis. J Antibiot 30:760–761Google Scholar
  56. Friedrich CG, Demain AL (1977b) Effects of lysine analogs on Penicillium chrysogenum. Appl Environ Microbiol 34:706–709Google Scholar
  57. Fujisawa Y, Kanzaki T (1975) Occurrence of a new cephalosporoate in a culture broth of a Cephalosporium acremonium mutant. J Antibiot 28:372–378PubMedGoogle Scholar
  58. Fujiasawa Y, Shirafuji H, Kida M, Nara K, Yoneda M, Kanzaki T (1973) New findings on cephalosporin C biosynthesis. Nature 246:154–155Google Scholar
  59. Fujiasawa Y, Shirafuji H, Kida M, Nara K, Yoneda M, Kanzaki T (1975) Accumulation of deacetylcephalosporin C by cephalosporin C negative mutants of Cephalosporium acremonium. Agric Biol Chem 39:1295–1301Google Scholar
  60. Fukase H, Hasegawa T. Hatano K, Iwasaki H, Yoneda M (1976) C-2801X, A new cephamycin-type antibiotic. J Antibiot 29:113–120Google Scholar
  61. Fuska S, Welwardova F (1969) Selection of productive strains of Penicillium chrysogenum. Biologia 24:691–698PubMedGoogle Scholar
  62. Godfrey OW (1973) Isolation of regulatory mutants of the aspartic and pyruvic acid families and their effect on antibiotic production in Streptomyces lipmanii. Antimicrob Agents Chemother 4:73–79PubMedGoogle Scholar
  63. Gorman M, Huber F (1977) β-Lactam antibiotics. In: Perlman D (ed) Annual Reports, Fermentation Processes, vol. 1. Academic Press, New York, pp 326–346Google Scholar
  64. Goulden SA, Chattaway FW (1969) End-product control of acetohydroxy acid synthetase by valine in Penicillium chrysogenum Q-176 and a high penicillin yielding mutant. J Gen Microbiol 59:111–118PubMedGoogle Scholar
  65. Grosklags JH, Swift ME (1957) The perfect stage of an antibiotic producing Cephalosporium. Mycologia 49:305–317Google Scholar
  66. Hasegawa T, Fukase H, Kitano K, Iwasaki H, Yoneda M (1975) Abstract - Annu Meet Agric Chem, Agricultural Soc. Japan, p 80Google Scholar
  67. Hashimoto M, Komori T, Kamiya T (1976) Nocardicin A, a new monocyclic β-lactam antibiotic. J Antibiot 29:890–901PubMedGoogle Scholar
  68. Higgens CE, Kastner RE (1971) Streptomyces clavuligerus sp. nov., a β-lactam antibiotic producer. Int J Syst Bacteriol 21:326–331Google Scholar
  69. Higgens EC, Hamill RL, Sands TH, Hoehn MM, Davis NE, Nagarajan R, Boeck LD (1974) The occurrence of deacetoxycephalosporin C in fungi and streptomycetes. J Antibiot 27:298–300PubMedGoogle Scholar
  70. Hosoda J, Konomi T, Tami N, Aoki H, Imanaka H (1977) Isolation of new nocardicins from Nocardia uniformis subsp. tsuyamanensis. Agric Biol Chem 41:2013–2020Google Scholar
  71. Huber FM, Baltz RH, Caltrider PG (1968) Formation of deacetylcephalosporin C in the cephalosporin C fermentation. Appl Microbiol 16:1011–1014PubMedGoogle Scholar
  72. Imada A, Nozaki Y, Kintaka, Okonogi K, Kitano K, Harada S (1980) C-19393 S2 and H2, new carbapenem antibiotics. I. Taxonomy of the producing strain, fermentation, and antibacterial properties. J Antibiot 33:1417–1424PubMedGoogle Scholar
  73. Imada A, Kitano K, Kintaka K, Mursi M, Asai M (1981) Sulfazecin and isosulfazecin, novel β-lactam antibiotics of bacterial origin. Nature 289:590–591PubMedGoogle Scholar
  74. Jeffery JDA, Abraham EP, Newton GGF (1961) Deacetylcephalosporin C. Biochem J 81:591–596PubMedGoogle Scholar
  75. Kahan JS, Kahan FM, Geogelman R, Currie SA, Jackson M, Stapley EO, Miller TW et al. (1976) Thienamycin: a new β-lactam antibiotic. I. Discovery and isolation. Abstract of papers, 16 th Intersci Conf Antimicrob Agents Chemother, no. 227. Ann Soc Microbiol, Washington, D.C.Google Scholar
  76. Kahan JS, Kahan FM, Geogleman R, Currie SA, Jackson M, Stapley EO, Miller TW et al. (1979) Thienamycin, a new β-lactam antibiotic. I. Discovery, taxonomy, isolation, and physical properties. J Antibiot 32:1–12PubMedGoogle Scholar
  77. Kamiya T (1977) Studies on the new monocyclic β-lactam antibiotics, Nocardicin A and B. In: Elks J (ed) Recent advances in the chemistry of β-lactam antibiotics (Special Publication No. 28). The Chemical Society, London, pp 281–294Google Scholar
  78. Kanzaki T, Fujisawa Y (1976) Biosynthesis of cephalosporin. Adv Appl Microbiol 20:159–202PubMedGoogle Scholar
  79. Kanzaki T, Fukita T, Shirafuji H, Fujisawa Y, Kitano K (1974) Occurrence of a 3-methylthiomethylcephem derivative in a culture broth of a Cephalosporium mutant. J Antibiot 27:361–362PubMedGoogle Scholar
  80. Kato K (1953) Occurrence of penicillin-nucleus in culture broths. J Antibiot Ser A 6:130136Google Scholar
  81. Kikuchi T, Uyeo S (1967) Pachysandra alkaloids. VIII. Structures of pachyoterminus-A and -B, novel type alkaloids having a β-lactam ring. Chem Pharm Bull 15:549–570PubMedGoogle Scholar
  82. Kitano K, Kintaka K, Suzuki S, Katamoto K, Nara K, Nakao Y (1975) Screening of microorganisms capable of producing β-lactam antibiotics. J Ferment Technol 53:327338Google Scholar
  83. Kitano K, Kintaka K, Nakao Y (1976) Some characteristics of β-lactam antibiotic-hypersensitive mutant derived from a strain of Pseudomonas aeruginosa. J Ferment Technol 54:696–704Google Scholar
  84. Kitano K, Nara K, Nakao Y (1977) Screening of β-lactam antibiotics using a mutant of Pseudomonas aeruginosa. J Antibiot [Suppl] 30:S239–5245Google Scholar
  85. Kohsaka M, Demain AL (1976) Conversion of penicillin N to cephalosporin(s) by cell-free extracts of Cephalosporium acremonium. Biochem Biophys Res Commun 70:465–473PubMedGoogle Scholar
  86. Komatsu KI, Kodaira R (1977) Sulfur metabolism of a mutant of Cephalosporium acremonium with enhanced potential to utilize sulfate for cephalosporin C production. J Antibiot (Tokyo) 30:226–233Google Scholar
  87. Komatsu KI, Mizuno M, Kodaira R (1975) Effect of methionine on cephalosporin C and penicillin N production by a mutant of Cephalosporium acremonium. J Antibiot 28:881–888PubMedGoogle Scholar
  88. Konomi T, Herschen S, Baldwin JE, Yoshida M, Hunt NA, Demain AL (1979) Cell-free conversion of d-(L-a-Aminoadipyl)-L-cysteinyl-D-valine into an antibiotic with the properties of isopenicillin N in Cephalosporium acremonium. Biochem J 184:427–430PubMedGoogle Scholar
  89. Krone B, Wanning M, Zähner H, Zeeck A (1981) Hydroxyethylclavam, a new antifungal β-lactam antibiotic (Abstr). 2nd Europ Cong Biotechnol, Eastbourne, England. Soc of Chem Indust, London, p 80Google Scholar
  90. Kurita M, Kazuyoshi J, Komori T, Miyairi M, Aoki H, Kuge S, Kamiya T, Imanaka H (1976) Isolation and characterization of nocardicin B. J Antibiot 29:1243–1245PubMedGoogle Scholar
  91. Lemke PA (1969) A century of compounds and their effect on fungi. Mycopathol Mycol Appl 38:49–59PubMedGoogle Scholar
  92. Lemke PA, Brannon DR (1972) Microbial synthesis of cephalosporin and penicillin compounds. In: Flynn EH (ed) Cephalosporins and penicillins, chemistry, and biology. Academic Press, New York, pp 370–437Google Scholar
  93. Lemke PA, Nash CH (1972) Mutations that affect antibiotic synthesis by Cephalosporium acremonium. Can J Microbiol 18:255–259PubMedGoogle Scholar
  94. Liersch M, Nüesch J, Treichler HJ (1976) Final steps in the biosynthesis of cephalosporin C. In: Macdonald KD (ed) Second international symposium on the genetics of industrial microorganisms. Academic Press, New York, pp 179–195Google Scholar
  95. Loder PB, Abraham EP (1971) Isolation and nature of intracellular peptides from a cephalosporin C producing Cephalosporium sp. Biochem J 123:471–476PubMedGoogle Scholar
  96. Macdonald KD (1972) Storage of conidia of Penicillium chrysogenum in liquid nitrogen. Appl Microbiol 23:990–993PubMedGoogle Scholar
  97. Marsluf GA (1970) Genetic and metabolic controls for sulfate metabolism in Neurospora crassa: isolation and study of chromate-resistant and sulfate-transport-negative mutants. J Bacteriol 102:716–721Google Scholar
  98. Masurekar PS, Demain AL (1974) Impaired penicillin production in lysine regulatory mutants of Penicillium chrysogenum. Antimicrob Agents Chemother 6:366–368PubMedGoogle Scholar
  99. Mehta RJ, Nash CH (1979) Relationship between carbon source and susceptibility of Cephalosporium acremonium to selected amino acid analogues. Can J Microbiol 25:818–821PubMedGoogle Scholar
  100. Miller IM, Stapley EO, Chaiet L (1962) Production of synnematin B by a member of the genus Streptomyces. Bacteriol Proc 32Google Scholar
  101. Miller TW, Geogeleman RT, Weston RG, Putter I, Wolf FJ (1972) Cephamycins, a new family of β-lactam antibiotics. Antimicrob Agents Chemother 2:132–135PubMedGoogle Scholar
  102. Morin RB, Jackson BG, Flynn EH, Roeske RW (1962) Chemistry of cephalosporin antibiotics. III. Chemical correlation of penicillin and cephalosporin antibiotics. J Am Chem Soc 84:3400–3401Google Scholar
  103. Morin RB, Jackson BG, Mueller RA, Lavagnino ER, Scanlon WB, Andrews SL (1963) Chemistry of cephalosporin antibiotics. III. Chemical correlation of penicillin and cephalosporin antibiotics. J Am Chem Soc 85:1896–1897Google Scholar
  104. Moyer AJ, Coghill RD (1946) Penicillin VIII. Production of penicillin in surface cultures. J Bacteriol 51:57–78Google Scholar
  105. Nagarajan R (1972) β-Lactam antibiotics from Streptomyces. In: Flynn EH (ed) Cephalosporins and penicillins. Academic Press, New York London, pp 636–661Google Scholar
  106. Nagarajan R, Boeck LD, Gorman M, Hamill RL, Higgens CE, Hoehn MM, Stark WM, Whitney JG (1971) β-lactam antibiotics from Streptomyces. J Am Chem Soc 93:2308–2310PubMedGoogle Scholar
  107. Nakayama M, Iwasaki A, Kimura S, Mizoguchi T, Tanabe S, Murakami A, Watanabe I, Okuchi M, Itoh H, Saino Y, Kobayashi F, Mori T (1980) Carpetimycins A and B, new β-lactam antibiotics. J Antibiot 33:1388–1390PubMedGoogle Scholar
  108. Nash CH, Huber FM (1971) Antibiotic synthesis and morphological differentiation of Cephalosporium acremonium. Appl Microbiol 22:6–10PubMedGoogle Scholar
  109. Nash CH, DeLaHiguera N, Neuss N, Lemke PA (1974) Application of biochemical genetics to the biosynthesis of β-lactam antibiotics. Dev Ind Microbiol 15:114–132Google Scholar
  110. Newton GGF, Abraham EP (1955) Cephalosporin C, a new antibiotic containing sulfur and D-a-aminoadipic acid. Nature 175:548–556PubMedGoogle Scholar
  111. Niss HF, Nash CH (1973) Synthesis of cephalosporin C from sulfate by mutants of Cephalosporium acremonium. Antimicrob Agents Chemother 4:474–478PubMedGoogle Scholar
  112. Nüesch J, Treichler HJ, Liersch M (1973) Biosynthesis of cephalosporin C. In: Vanek Z, Hostalek Z, Cudlin J (eds) Genetics of industrial microorganisms, vol 2. Elsevier, Amsterdam, pp 309–334Google Scholar
  113. Okamura K, Hirata S, Okumura V, Fukagawa Y, Shimauchi Y, Kouno K, Ishikura T, Lein J (1978) PS-5, a new β-lactam antibiotic from Streptomyces. J Antibiot 31:480–482PubMedGoogle Scholar
  114. Okamura K, Hirata S, Koki A, Hori K, Shibamoto N, Okamura Y, Okabe M et al. (1979 a) PS-5, a new β-lactam antibiotic. I. Taxonomy of the producing organism, isolation and physico-chemical properties. J Antibiot 32:262–271Google Scholar
  115. Okamura K, Koki A, Sakamoto M, Kubo K, Mutoh Y, Fukagawa Y, Kouno K et al. (1979b) Microorganisms producing a new β-lactam antibiotic. J Ferment Technol 57:265–272Google Scholar
  116. Okanishi M, Gregory KF (1970) Isolation of mutants of Candida tropicales with increased methionine concentration. Can J Microbiol 16:1139–1143PubMedGoogle Scholar
  117. Olson BH, Jennings JC, Junek AJ (1953) Separation of synnematin into components A and B by paper chromatography. Science 117:76–78PubMedGoogle Scholar
  118. Omura S, Tanaka H, Oiwa R, Nagai T, Koyama Y, Takahashi S (1979) Studies on bacterial cell wall inhibitors VI. Screening method for the specific inhibitors of peptidoglycan synthesis. J Antibiot 32:978–984PubMedGoogle Scholar
  119. Pan CH, Hepler L, Elander RP (1972) Control of pH and carbohydrate addition in the penicillin fermentation. Dev Ind Microbiol 13:103–112Google Scholar
  120. Pan CH, Hepler L, Elander RP (1975) The effect of iron on a high-yielding industrial strain of Penicillium chrysogenum. J Ferment Technol 53:854–861Google Scholar
  121. Perlman D, Kikuchi M (1977) Culture maintenance. In: Perlman D (ed) Annual reports, fermentation processes, vol. 1. Academic Press, New York, pp 41–48Google Scholar
  122. Pisano MA, Vellozzi EM (1974) Production of cephalosporin C by Paecilomyces persicinus P-10. Antimicrob Agents Chemother 6:447–451PubMedGoogle Scholar
  123. Preuss DL, Johnson MJ (1967) Penicillin acyltransferase in Penicillium chrysogenum. J Bacteriol 94:1502–1508Google Scholar
  124. Queener SW, Capone JJ (1974) Deacetoxycephalosporin C accumulation in mutants of Cephalosporium acremonium. (Abstr) Genetics of Indust Microorganisms. Academic Press, London, p 33Google Scholar
  125. Queener SW, McDermott JJ, Radue AB (1975) Glutamate dehydrogenase-specific activity and cephalosporin synthesis in the M8650 series of Cephalosporium acremonium mutants. Antimicrob Agents Chemother 7:646–651PubMedGoogle Scholar
  126. Raper KB, Fennell DA (1946) The production of penicillin in submerged culture. J Bacteriol 51:761–777Google Scholar
  127. Raper KB, Alexander DF, Coghill RD (1944) Penicillin I. Natural variation and penicillin production in Penicillium notatum and allied species. J Bacteriol 48:639–659PubMedGoogle Scholar
  128. Reading E, Cole M (1977) Clavulanic acid: a beta-lactamase inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 11:852–857PubMedGoogle Scholar
  129. Roberts JM (1952) Antibiotics produced by species of Cephalosporium, with a description of a new species. Mycologia 44:292–306Google Scholar
  130. Rode LJ, Foster JW, Schuhardt VT (1947) Penicillin production by a thermophilic fungus. J Bacteriol 53:565–572Google Scholar
  131. Rosi D, Drozd ML, Kuhrt MF, Terminello L, Came PE, Daum SJ (1981) Mutants of Streptomyces cattleya producing N-acetyl and deshydroxy carbapenems related to thienamycin. J Antibiot 34:341–342PubMedGoogle Scholar
  132. Sanders AG (1949) In: Florey HW, Chain EB, Heatley NG, Jennings MA, Sanders AG, Abraham EP, Florey ME (eds) Antibiotics, vol 2. Oxford University Press, London New York, pp 672–685Google Scholar
  133. Scannell JP, Pruess DL, Blount JF, Ax HA, Kellet M, Weiss F, Demmy TC, Williams TH, Stempel A (1975) Antimetabolites produced by microorganisms XIII. (S)-alanyl-3-[a(S)-chloro-3(S)-hydroxy-2-oxo-3-azetidinymethyl]-(S) alanine, a new β-lactam containing a natural product. J Antibiot 28:1–6PubMedGoogle Scholar
  134. Segel IH, Johnson MJ (1961) Accumulation of intracellular sulfate by Penicillium chrysogenum. J Bacteriol 81:91–98PubMedGoogle Scholar
  135. Sheehan JC, Henery-Logan KR (1959) A general synthesis of the penicillins. J Am Chem Soc 81:5838–5839Google Scholar
  136. Smith B, Warren SC, Newton GGF, Abraham EP (1967) Biosynthesis of penicillin N and cephalosporin C. Biochem J 103:877–890Google Scholar
  137. Spratt BG (1977) Properties of the penicillin-binding proteins of Escherichia coli K12. Eur J Biochem 72:341–352PubMedGoogle Scholar
  138. Stapley EO, Jackson M, Hernandez S, Zimmerman SB, Currie SA, Mochales S, Mata JM, Woodruff HB, Hendlin D (1972) Cephamycins, a new family of β-lactam antibiotics. I. Production by actinomycetes, including Streptomyces lactamdurans, sp. n. Antimicrob Agents Chemother 2:122–131PubMedGoogle Scholar
  139. Stapley EO, Cassidy P, Currie SA, Daoust D, Goegelman R, Hernandez S, Jackson M et al. (1977) Epithienamycins: Biological studies of a new family of β-lactam antibiotics. Abst Intersci Conf Antimicrob Ag Chemother 17 th, New York, Paper No. 80, Amer Soc Microbiol, Washington, D.C., 20006Google Scholar
  140. Stewart WW (1971) Isolation and proof of structure of wildfire toxin. Nature 229:174–178PubMedGoogle Scholar
  141. Sykes RB, Cimarusti CM, Bonner DP, Bask K, Floyd DM, Georgopapadakou NH, Koster WH et al. (1981) Monocyclic β-lactam antibiotics produced by bacteria. Nature 291:489–491PubMedGoogle Scholar
  142. Swartz RW (1979) The use of economic analysis of penicillin G manufacturing costs in establishing priorities for fermentation process improvement. Abstr ACS Meeting, 176th, Miami Beach, September 1978Google Scholar
  143. Tamaki S, Nakagawa JI, Marugama IN, Matsuhashi M (1978) Supersensitivity to β-lactam antibiotics in Escherichia coli caused by a D-alanine carboxypeptidase lA mutation. Agric Biol Chem 42:2147–2150Google Scholar
  144. Taylor PA, Schnoes HK, Durbin RD (1972) Characterization of chlorosis inducing toxins from a plant pathogenic Pseudomonas sp. Biochim Biophys Acta 286:107–117PubMedGoogle Scholar
  145. Traxler P, Treichler HJ, Nüesch J (1975) Synthesis of N-acetyldeacetoxycephalosphorin C by a mutant of Cephalosporium acremonium. J Antibiot 28:605–606PubMedGoogle Scholar
  146. Treichler HJ, Liersch M, Nüesch J (1978) Genetics and biochemistry of cephalosporin biosynthesis. In: Hütter R, Leisinger T, Nüesch J, Wehrli W (eds) Antibiotics and other secondary metabolites. Academic Press, New York, pp 177–199Google Scholar
  147. Treichler HJ, Liersch M, Nüesch J, Dobeli H (1979) Role of sulphur metabolism in cephalosporin C and penicillin biosynthesis. In: Sebek OK, Laskin AI (eds) Genetics of industrial microorganisms. American Society of Microbiology, Washington, D.C., pp 97–104Google Scholar
  148. Trilli A, Michelini V, Mantovani V, Pirt SJ (1978) Development of the agar disc method for the rapid selection of cephalosporin producers with improved yield. Antimicrob Agents Chemother 13:7–13PubMedGoogle Scholar
  149. Troonen H, Roelants P, Boon B (1976) RIT 2214, a new biosynthetic penicillin produced by a mutant of Cephalosporium acremonium. J Antibiot 29:1258–1266PubMedGoogle Scholar
  150. Tubaki K (1973) Aquatic sediment as a habitat of Emericellopsis, with a description of an undescribed species of Cephalosporium. Mycologia 65:938–941Google Scholar
  151. Uri J, Valer G, Bekesi I (1963) Production of 6-aminopenicillanic acid by dermatophytes. Nature 200:896–897PubMedGoogle Scholar
  152. Wellman AM, Stewart GW (1973) Storage of brewing yeasts by liquid nitrogen preservation. Appl Microbiol 26:577–583PubMedGoogle Scholar
  153. Wesseling AC, Lago BD (1981) Strain improvement of cephamycin producers, Nocardia lactamdurans and Streptomyces griseus. Dev Ind Microbiol 22:641–651Google Scholar
  154. Woodward RB, Heusler K, Gosteli J, Naegele P, Oppolzer W, Ramage R, Ranganathan S, Vorbruggen H (1966) The total synthesis of cephalosporin C. J Am Chem Soc 88:852–853Google Scholar

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© Springer-Verlag Berlin Heidelberg 1983

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  • R. P. Elander

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