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Expansion of Gamma-Butyrolactone Signaling Molecule Biosynthesis to Phosphotriester Natural Products
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-11-24 , DOI: 10.1021/acschembio.0c00824
Yuta Kudo 1, 2, 3 , Takayoshi Awakawa 1, 4 , Yi-Ling Du 5 , Peter A Jordan 1 , Kaitlin E Creamer 1 , Paul R Jensen 1 , Roger G Linington 6 , Katherine S Ryan 5 , Bradley S Moore 1, 7
Affiliation  

Bacterial hormones, such as the iconic gamma-butyrolactone A-factor, are essential signaling molecules that regulate diverse physiological processes, including specialized metabolism. These low molecular weight compounds are common in Streptomyces species and display species–specific structural differences. Recently, unusual gamma-butyrolactone natural products called salinipostins were isolated from the marine actinomycete genus Salinispora based on their antimalarial properties. As the salinipostins possess a rare phosphotriester motif of unknown biosynthetic origin, we set out to explore its construction by the widely conserved 9-gene spt operon in Salinispora species. We show through a series of in vivo and in vitro studies that the spt gene cluster dually encodes the salinipostins and newly identified natural A-factor-like gamma-butyrolactones (Sal-GBLs). Remarkably, homologous biosynthetic gene clusters are widely distributed among many actinomycete genera, including Streptomyces, suggesting the significance of this operon in bacteria.

中文翻译:

将γ-丁内酯信号分子生物合成扩展为磷酸三酯天然产物

细菌激素,例如标志性的 γ-丁内酯 A 因子,是必不可少的信号分子,可调节多种生理过程,包括专门的新陈代谢。这些低分子量化合物在链霉菌属物种中很常见,并显示出物种特异性的结构差异。最近,基于它们的抗疟特性,从海洋放线菌属Salinispora中分离出了一种不寻常的γ-丁内酯天然产物,称为盐碱贴素。由于salinipostins 具有未知生物合成来源的罕见磷酸三酯基序,我们着手探索其在盐孢属物种中广泛保守的9 基因spt操纵子的构建。我们通过一系列的体内展示体外研究,该SPT基因簇双重编码salinipostins和新鉴定的天然A-因子样的γ-丁内酯(SAL-GBLS)。值得注意的是,同源生物合成基因簇广泛分布在包括链霉菌在内的许多放线菌属中,表明该操纵子在细菌中的重要性。
更新日期:2020-12-18
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