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Rebeccamycin

Rebeccamycin (NSC 655649) is a weak topoisomerase I inhibitor isolated from Nocardia bacteria. It is structurally similar to staurosporine, but does not show any inhibitory activity against protein kinases. It shows significant antitumor properties in vitro (IC50=480nM against mouse B16 melanoma cells and IC50=500nM against P388 leukemia cells). It is an antineoplastic antibiotic and an intercalating agent.

Biosynthesis
An early step in the biosynthesis is the reaction of 7-chloro-L-tryptophan with oxygen catalysed by 7-chloro-L-tryptophan oxidase (RebO): Dichlorochromopyrrolate synthase (RebD) couples two molecules of the intermediate 2-iminio-3-(7-chloroindol-3-yl)propionate to give dichlorochromopyrrolic acid: The enzyme dichloroarcyriaflavin A synthase is responsible for forming the new aromatic bond between the indole components of dichlorochromopyrrolic acid, making a six-membered ring. The reaction proceeds in two stages. A protein component, called RebP, is an oxidase which contains heme and uses oxygen and nicotinamide adenine dinucleotide (NADH) to link the rings. Then it acts with a flavin-dependent partner called RebC to remove the two carboxylic acid groups by oxidative decarboxylation. The penultimate step in rebeccamycin's biosynthesis is the addition of a sugar group to one of the indole nitrogens by 4'-demethylrebeccamycin synthase (RebG). The final methylation is carried out by demethylrebeccamycin-D-glucose O-methyltransferase (RebM) using S-adenosyl methionine as cofactor. == References ==
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