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

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 co...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2012-08, Vol.134 (30), p.12434-12437
Main Authors: Yamanaka, Kazuya, Ryan, Katherine S, Gulder, Tobias A. M, Hughes, Chambers C, Moore, Bradley S
Format: Article
Language:English
Subjects:
Catalysis
Flavin-Adenine Dinucleotide - analogs & derivatives
Flavin-Adenine Dinucleotide - metabolism
Genes, Bacterial
Multigene Family
Oxidoreductases - genetics
Oxidoreductases - metabolism
Pyrroles - chemistry
Pyrroles - metabolism
Streptomyces - chemistry
Streptomyces - enzymology
Streptomyces - genetics
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja305670f