Fusarium merismoides Corda NR 6356, the source of the protein kinase C inhibitor, azepinostatin. Taxonomy, yield improvement, fermentation and biological activity.
Fungal strain NR 6356, Fusarium merismoides Corda, was discovered as the source of the protein kinase C (PKC) inhibitor, azepinostatin. The strain was identified based on its growth on potato sucrose agar, slender conidial shape, characteristic polyphialide and production of abundant chlamydospores. Fusarium aquaeductuum Lagh. IMI 103658 and Fusarium sp. NR 7222 were also found to produce the same inhibitor. After single colony isolation and medium optimization trials, a more than 30-fold increase in the production of azepinostatin over the original culture was achieved. Azepinostatin selectively and potently inhibited rat brain PKC with an IC50 value of 70 nM. Other enzymes utilizing ATP, including hexokinase, were not affected. The Ki of azepinostatin for PKC was 0.5 nM. The inhibition of PKC was competitive with ATP and uncompetitive with histone.
Nippon Roche Research Center, Kanagawa, Japan.
S
S
Ohshima
M
M
Yanagisawa
A
A
Katoh
T
T
Fujii
T
T
Sano
S
S
Matsukuma
T
T
Furumai
M
M
Fujiu
K
K
Watanabe
K
K
Yokose
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005285:Fermentation; D005670:Fusarium / Q000145:classification / Q000254:growth & development / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D001381:Azepines; D003470:Culture Media; D062385:Hydroxybenzoates; C088497:azepinostatin; D011493:Protein Kinase C