Abstract
Micromonospora sp C39500, isolated in our laboratory from a soil sample, produced a complex of seven novel depsipeptide antitumor antibiotics, designated korkormicins. The major component of the complex, korkormicin A, has a MW of 1452 and a molecular formula of C66H84N16O22. Korkormicin A exhibits potentin vivo antitumor activity against P388 leukemia and M109 lung carcinoma implanted intraperitoneally (ip) in mice, with effective doses of 0.05–0.20 mg kg−1 injection−1, for five or three ip injections, respectively. It is also active against Gram-positive bacteria but inactive against Gram-negative bacteria. The production of korkormicin A was enhanced by 3-fold when 0.1%l-valine was added to the production culture at 48h. A titer of 401.0 μg ml−1 was achieved in the fermenter culture supplemented with 0.1%l-valine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Becker B, MP Lechevalier and HA Lechevalier. 1965. Chemical composition of cell-wall preparations from strains of various form-genera of aerobic actinomycetes. Appl Microbiol 13:236–243
Dell A, DH Williams, HR Morris, GA Smith, J Feeney and GCK Roberts. 1975. Structure revision of antibiotic echinomycin. J Am Chem Soc 97:2497–2502.
Fox KR, H Davies, GR Adams, J Portugal and MJ Waring. 1988. Sequence-specific binding of luzopeptin to DNA. Nucleic Acid Res 16:2489–2507.
Gauvreau D and MJ Waring. 1984. Directed biosynthesis of novel derivatives of echinomycin byStreptomyces echinatus. I. Effect of exogenous analogues of quinoxaline-2-carboxylic acid on the fermentation. Can J Microbiol 30:439–450.
Gauvreau D and MJ Waring. 1984. Directed biosynthesis of novel derivatives of echinomycin. II. Purification and structure elucidation. Can J Microbiol 30:730–738.
Geran RI, NH Greenberg, MM MacDonald, AM Schumacher and BJ Abbott. 1972. Protocols for screening chemical agents and natural products against tumors and other biological systems. Cancer Chemother Rep (Part 3) 3:1–103.
Huang C-H and ST Crooke. 1986. Effects of structural modifications of anti-tumor antibiotics luzopeptins on cell growth and macromolecule biosynthesis. Anti-Cancer Drug Design 1:87–94.
Huang C-H, S Mong and ST Crooke. 1980. Inferations of a new antitumor antibiotic BBM-928A with deoxyribonucleic acid. Bifunctional intercalative binding studied by fluorometry and viscometry. Biochemistry 19:5537–5542.
Huang C-H, AW Prestayko and ST Crooke. 1982. Bifunctional intercalation of antitumor antibiotics BBM-928A and echinomycin with deoxyribonucleic acid. Effects of intercalation on deoxyribonucleic acid degradative activity of bleomycin and phleomycin. Biochemistry 21:3704–3710.
Konishi M, H Ohkuma, F Sakai, T Tsuno, H Koshiyama, T Naito and H Kawaguchi. 1981. BBM-928, a new antitumor antibiotic complex III. Structure determination of BBM-928 A, B and C. J Antibiot 34: 148–159.
Matson JA and JA Bush. 1989. Sandramycin, a novel antitumor antibiotic produced by aNocardioides sp. Production, isolation, characterization and biological properties. J Antibiot 42:1763–1767.
Matson JA, KL Colson, GN Belofsky and BB Bleiberg. 1993. Sandramycin, a novel antitumor antibiotic produced by aNocardioides sp. II. Structure determination. J Antibiot 46:162–166.
Ohkuma H, F Sakai, Y Nishiyama, M Ohbayashi, H Imanishi, M Konishi, T Miyaki, H Koshiyama and H Kawaguchi. 1980. BBM-928, a new antitumor actibiotic complex. I. Production, isolation, characterization and antitumor activity. J Antibiot 33:1087–1097.
Rhodes A and DL Fletcher. 1966. Principles of Industrial Microbiology. Ch 6. Pergamon, New York.
Rose WC. 1981. Evaluation of Madison 109 lung carcinoma as a model for screening antitumor drugs. Cancer Treatment Rep 65: 299–312.
Rose WC, JE Schurig, JB Hoftalen and WT Bradner. 1983. Experimental antitumor activity and toxicity of a new chemotherapeutic agent, BBM-928A. Cancer Research 43:1504–1510.
Sokatch JR. 1969. Bacterial Physiology and Metabolism. Ch 11. Academic Press, New York.
Tomita K, Y Hoshino, T Sasahira and H Kawaguchi. 1980. BBM-928, a new antitumor antibiotic complex. II. Taxonomic studies on the producing organism. J Antibiot 33:1098–1102.
Waring MJ and KR Fox. 1983. Molecular aspects of the interaction between quinoxaline antibiotics and nucleic acids. In: Molecular Aspects of Anti-cancer Drug Action (S Neidle and MJ Waring, eds), pp 127–156, Macmillan Press, Houndmills, UK.
Waring MJ and LPG Wakelin. 1974. Echinomycin: a bifunctional intercalating antibiotic. Nature 252:653–657.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lam, K.S., Gustavson, D.R., Hesler, G.A. et al. Korkormicins, novel depsipeptide antitumor antibiotics fromMicromonospora sp C39500: Fermentation, precursor directed biosynthesis and biological activities. Journal of Industrial Microbiology 15, 60–65 (1995). https://doi.org/10.1007/BF01570015
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01570015