Flavin-dependent halogenases (FDHs) are known for installing halogens on natural products. To date, most reported FDHs are two-component FDHs, which require a flavin reductase as the reaction partner to function. Here, we report the identification of a new halogenated biaryl compound 2-chloro venemycin (1) through constitutive expression of the regulator gene vemR in the vem gene cluster in Streptomyces sp. S006 and media optimization. In addition, we provide biochemical evidence that, in the absence of the flavin reductase, purified FDH VemK catalyzes the regioselective halogenation of the pyrone moiety of venemycin (2). Mutagenesis studies showed that T315 and R317 residues are likely crucial for catalysis and NAD(P)H binding. VemK represents the first characterized single-component FDH from Streptomyces and the first FDH that halogenates a pyrone moiety.

中文翻译：

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在Venemycins的生物合成中，单组分黄素酶催化吡喃酮的区域选择性卤代反应。

依赖黄素的卤化酶（FDHs）可以在天然产物中安装卤素。迄今为止，大多数报道的FDH是两组分FDH，需要黄素还原酶作为反应伴侣才能发挥作用。在这里，我们报告通过链霉菌属sp的vem基因簇中调控基因vemR的组成型表达，鉴定出一种新的卤代联芳基化合物2-氯韦霉素（1）。S006和媒体优化。此外，我们提供的生化证据表明，在没有黄素还原酶的情况下，纯化的FDH VemK可以催化凡尼霉素（2）吡喃酮部分的区域选择性卤化。诱变研究表明，T315和R317残基可能对催化和NAD（P）H结合至关重要。