Flavoenzyme-Catalyzed Atropo-Selective N,C-Bipyrrole Homocoupling in Marinopyrrole Biosynthesis

Citation:
Yamanaka, K, Ryan KS, Gulder TAM, Hughes CC, Moore BS.  2012.  Flavoenzyme-Catalyzed Atropo-Selective N,C-Bipyrrole Homocoupling in Marinopyrrole Biosynthesis. Journal of the American Chemical Society. 134:12434-12437.

Date Published:

Aug

Keywords:

cytochrome-p450, enzyme, gene-cluster, streptomyces sp

Abstract:

Axially chiral biaryl compounds are frequently encountered in nature where they exhibit diverse biological properties. Many are biphenols that have C-C or C-O linkages installed by cytochrome P450 oxygenases that control the regio- and stereoselectivity of the intermolecular coupling reaction. In contrast, bipyrrole-coupling enzymology has not been observed. Marinopyrroles, produced by a marine-derived streptomycete, are the first 1,3'-bipyrrole natural products. On the basis of marinopyrrole's unusual bipyrrole structure, we explored its atropo-selective biosynthesis in Streptomyces sp. CNQ-418 in order to elucidate the N,C-bipyrrole homocoupling enzymology. Through a series of genetic experiments involving the discovery and heterologous expression of marinopyrrole biosynthesis genes, we report that two flavin-dependent halogenases catalyze the unprecedented homocoupling reaction.

Notes:

n/a

Website

DOI:

10.1021/ja305670f