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Published on: February 7, 2019
Enzymatic assembly of the bis-indole core of rebeccamycin
Tomoyasu Nishizawa1, Sabine Grüschow, Don-Hema E Jayamaha
1Department of Medicinal Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Abstract:
Rebeccamycin is a member of the family of indolocarbazole antibiotics with broad spectrum antitumor activity. The indolocarbazole framework is derived from two molecules of tryptophan, but very little is known about the enzymes involved in rebeccamycin biosynthesis. Here, we show that RebD is responsible for all catalytic steps forming the central pyrrole ring of chlorochromopyrrolic acid from two molecules of chloroindolepyruvic acid. This transformation does not require any additional cofactors and constitutes the first step of bis-indole formation in the biosynthesis of rebeccamycin.
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