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 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.
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093, United States.
Kazuya
K
Yamanaka
Katherine S
KS
Ryan
Tobias A M
TA
Gulder
Chambers C
CC
Hughes
Bradley S
BS
Moore
D002384:Catalysis; D005182:Flavin-Adenine Dinucleotide / Q000031:analogs & derivatives* / Q000378:metabolism; D005798:Genes, Bacterial; D005810:Multigene Family; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics
D011758:Pyrroles; D005182:Flavin-Adenine Dinucleotide; C058805:1,5-dihydro-FAD; D010088:Oxidoreductases