ACS Chem Biol. 2010 Jul 16;5(7):659-65. doi: 10.1021/cb100117k.
Bacterially produced small molecules demonstrate a remarkable range of structural and functional diversity and include some of our most useful biological probes and therapeutic agents. Annotations of bacterial genomes reveal a large gap between the number of known small molecules and the number of biosynthetic genes/loci that could produce such small molecules, a gap that most likely originates from tight regulatory control by the producing organism. This study coupled a global transcriptional regulator, HexA, to secondary metabolite production in Photorhabdus luminescens, a member of the Gammaproteobacteria that participates in a complex symbiosis with nematode worms and insect larvae. HexA is a LysR-type transcriptional repressor, and knocking it out to create a P. luminescens DeltahexA mutant led to dramatic upregulation of biosynthesized small molecules. Use of this mutant expanded a family of stilbene-derived small molecules, which were known to play important roles in the symbiosis, from three members to at least nine members.
细菌产生的小分子表现出显著的结构和功能多样性，其中包括一些我们最有用的生物探针和治疗剂。对细菌基因组的注释表明，已知小分子的数量与能够产生此类小分子的生物合成基因/基因座的数量之间存在很大差距，这种差距很可能源自产生生物体的严格调控控制。这项研究将全局转录调节剂 HexA 与 Photorhabdus luminescens 的次级代谢产物生产偶联在一起， Photorhabdus luminescens 是γ变形菌的成员，与线虫和昆虫幼虫参与复杂的共生关系。HexA 是一种 LysR 型转录阻遏物，敲除它会导致 P. luminescens DeltahexA 突变体中小分子生物合成的显著上调。该突变体的使用将stilbene 衍生的小分子家族从已知在共生中起重要作用的三个成员扩展到至少九个成员。
