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 sampl e, produced a complex of seven novel depsipeptide antitumor antibiotic s, designated korkormicins. The major component of the complex, korkor micin A, has a MW of 1452 and a molecular formula of C66H84N16O22. Kor kormicin A exhibits potent in vivo antitumor activity against P388 leu kemia 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-p ositive bacteria but inactive against Gram-negative bacteria. The prod uction 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 mu g ml(-1) was achieved in the fermenter culture supplemented with 0.1% L-valine.