The Shurosporine Producing Strain Streptomyces longisporoflavus Produces Metabolites Related to K-252a. Proposal for Biosynthetic Intermediates of K-252a.

The Journal of Antibiotics
1996.0

Abstract

Alkaloids of the indolocarbazole type bind to ATP-binding sites of various enzymes. Staurosporine isolated from Saccharothrix aerocolonigenes subsp. staurosporeus1) was found to be an inhibitor of protein kinase C (PKC) in the low nanomolar range2). Most other alkaloids of this type contain a six-membered sugar moiety like staurosporine3-6). A subgroup of these metabolites are K-252a (6)7) and K-252b8), which were isolated by Japanese researchers from two Nocardiopsis species strains as PKC inhibitors. In contrast to staurosporine these secondary metabolites have a five-membered sugar moiety and a carboxylate function attached to this ring. Although a weaker inhibitor of PKC than staurosporine, K-252b attracted considerable interest as it is able to potentiate neurotrophin-3 actions in vitro9). In previous publications we described several minor metabolites of Streptomyces longisporoflavus strain R-19 which were isolated as byproducts of a large scale staurosporine fermentation6,10). In the present communication the structure elucidation, physicochemical data, and biological properties of further minor metabolites are described. Fermentation6) and isolation10) of the new compounds were reported earlier.

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