Korkormicins, novel depsipeptide antitumor antibiotics from Micromonospora sp C39500: fermentation, precursor directed biosynthesis and biological activities.
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 potent in 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 48 h. A titer of 401.0 micrograms ml-1 was achieved in the fermenter culture supplemented with 0.1% L-valine.
Lam
K S
KS
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
Gustavson
D R
DR
Hesler
G A
GA
Dabrah
T T
TT
Matson
J A
JA
Berry
R L
RL
Rose
W C
WC
Forenza
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy; D003470:Culture Media / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005285:Fermentation / Q000187:drug effects / Q000502:physiology; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008847:Micromonospora / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D009584:Nitrogen / Q000494:pharmacology; D014633:Valine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D014633:Valine; D009584:Nitrogen