FUSARIUM-MERISMOIDES CORDA NR-6356, THE SOURCE OF THE PROTEIN-KINASE-C INHIBITOR, AZEPINOSTATIN - TAXONOMY, YIELD IMPROVEMENT, FERMENTATIONAND BIOLOGICAL-ACTIVITY

Fungal strain NR 6356, Fusarium merismoides Corda, was discovered as t he source of the protein kinase C (PKC) inhibitor, azepinostatin. The strain was identified based on its growth on potato sucrose agar, slen der conidial shape, characteristic polyphialide and production of abun dant chlamydospores. Fusarium aquaeductuum Lagh. IMI 103658 and Fusari um sp. NR 7222 were also found to produce the same inhibitor. After si ngle colony isolation and medium optimization trials, a more than 30-f old increase in the production of azepinostatin over the original cult ure was achieved. Azepinostatin selectively and potently inhibited rat brain PKC with an IC50 value of 70 nM. Other enzymes utilizing ATP, i ncluding hexokinase, were not affected. The Ki of azepinostatin for PK C was 0.5 nM. The inhibition of PKC was competitive with ATP and uncom petitive with histone.