Production of the Staurosporine Aglycon K-252c with a Blocked Mutant of the Staurosporine Producer Strain Streptomyces longisporoflavus and by Biotransformation of Staurosporine with Streptomyces mediocidicus ATCC 13279.

The Journal of Antibiotics
1995.0

Abstract

Staurosporine (1) was first isolated in 1977 by Omura et al. from Streptomyces staurosporeus. About 10 years later in 1986, Nakanishi et al. reported the first isolation of K-252c, the staurosporine aglycon moiety, from the culture broth of Nocardiopsis sp. K-2902. K-252c (2) acts like staurosporine as an inhibitor of protein kinase C. While studying the mechanism of action of this indolocarbazole compound, it appeared, that the interactions between the protein kinase and this kind of alkaloids were due to the rigid aromatic ring. The fact, that the aromatic system is important for the inhibition of the kinase activity, suggests that other indolcarbazoles may develop interesting biological activity. In the course of our screening program for staurosporine metabolites two original ways for the production of the staurosporine aglycon moiety K-252c (2) could be demonstrated. Compound (2) could be achieved with a blocked mutant of the staurosporine producer strain Streptomyces longisporoflavus R19/ col15 (TU 2399) and via biotransformation of staurosporine with Streptomyces mediocidicus ATCC13279.

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