Flavoenzyme-catalyzed atropo-selective N,C-bipyrrole homocoupling in marinopyrrole biosynthesis.
Flavoenzyme-catalyzed atropo-selective N,C-bipyrrole homocoupling in marinopyrrole biosynthesis.
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DOI：
10.1021/ja305670f
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发表时间：
2012-08-01
影响因子：
15
通讯作者：
Moore BS
中科院分区：
文献类型：
--
作者：
Yamanaka K;Ryan KS;Gulder TA;Hughes CC;Moore BS
轴向手性联芳基化合物是自然界中常见的一类化合物，具有多种生物学性质。许多是具有由细胞色素P450加氧酶安装的C-C或C-O键的联苯酚，所述细胞色素P450加氧酶控制分子间偶联反应的区域和立体选择性。相反，联吡咯偶联酶学尚未观察到。Marinopyrroles是由海洋链霉菌产生的第一个1，3 ′-bipyrrole天然产物.基于marinopyrrole独特的联吡咯结构，我们研究了其在链霉菌CNQ-418中的阿托品选择性生物合成，以阐明N，C-联吡咯同源偶联酶的酶学性质。通过一系列涉及marinopyrrole生物合成基因的发现和异源表达的遗传实验，我们报告说，两个黄素依赖性卤代酶催化前所未有的homocoupling反应。
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.