UCN-01 and UCN-02, new selective inhibitors of protein kinase C. I. Screening, producing organism and fermentation.
In the course of continued screening program for new selective inhibitors of protein kinase C (PKC), fermentation broths from over 5,000 soil isolates were screened for their inhibitory activity of PKC. HPLC analysis of active cultures revealed that five different strains (N-71, N-115, N-126, N-128 and N-139) of Streptomyces isolated from various local soil samples were found to produce staurosporine and related compounds. Of these strains, N-126, a high producing strain, was found to produce new selective inhibitors of PKC, UCN-01 and its stereoisomer, UCN-02. The pH control of fermentation resulted in an increase of the production of UCN-01 and UCN-02.
Takahashi
I
I
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan.
Asano
K
K
Kawamoto
I
I
Tamaoki
T
T
Nakano
H
H
D000470:Alkaloids / Q000096:biosynthesis*; D002473:Cell Wall / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D005285:Fermentation; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D008855:Microscopy, Electron, Scanning; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012988:Soil Microbiology; D019311:Staurosporine / Q000031:analogs & derivatives; D013302:Streptomyces / Q000145:classification / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure
D000470:Alkaloids; D003470:Culture Media; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine