Pyrazines are important structures widely found in many known drugs. The biological approaches for their synthesis were poorly applied. Herein, microbial production of several halogenated diphenyl pyrazines is reported. These compounds are accumulated via feeding corresponding precursor analogs to Escherichia coli expressing a fungal non-ribosomal peptide synthetase HqlA. Substrate specificity of HqlA was also determined by comparing substrate incorporation efficiencies. HqlA requires a C4-hydroxyl in the substrate and can tolerate certain degrees of size change on the substitution at the carbon next to the hydroxyl group.

中文翻译：

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用青霉青霉单模块真菌非核糖体肽合成酶在大肠杆菌中制备新的卤代二苯基吡嗪类似物

吡嗪是在许多已知药物中广泛发现的重要结构。合成它们的生物学方法应用不善。在此，报道了几种卤代二苯基吡嗪的微生物生产。这些化合物是通过将相应的前体类似物喂入表达真菌非核糖体肽合成酶HqlA的大肠杆菌中而积累的。还通过比较底物掺入效率来确定HqlA的底物特异性。HqlA在底物中需要一个C4-羟基，并且可以耐受羟基旁碳原子取代时一定程度的尺寸变化。