International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Marine Resource Science, Faculty of Agriculture and Marine Science, Kochi University, 200 Otsu, Monobe, Nankoku, Kochi, 783-8502, Japan.
J Ind Microbiol Biotechnol. 2018 Feb;45(2):77-87. doi: 10.1007/s10295-017-1997-x. Epub 2017 Dec 18.
The genome of streptomycetes has the ability to produce many novel and potentially useful bioactive compounds, but most of which are not produced under standard laboratory cultivation conditions and are referred to as silent/cryptic secondary metabolites. Streptomyces lavendulae FRI-5 produces several types of bioactive compounds. However, this strain may also have the potential to biosynthesize more useful secondary metabolites. Here, we activated a silent biosynthetic gene cluster of an uncharacterized compound from S. lavendulae FRI-5 using heterologous expression. The engineered strain carrying the silent gene cluster produced compound 5, which was undetectable in the culture broth of S. lavendulae FRI-5. Using various spectroscopic analyses, we elucidated the chemical structure of compound 5 (named lavendiol) as a new diol-containing polyketide. The proposed assembly line of lavendiol shows a unique biosynthetic mechanism for polyketide compounds. The results of this study suggest the possibility of discovering more silent useful compounds from streptomycetes by genome mining and heterologous expression.
放线菌的基因组能够产生许多新型且具有潜在用途的生物活性化合物，但其中大多数在标准实验室培养条件下都不会产生，这些化合物被称为沉默/隐性次级代谢产物。弗氏链霉菌 FRI-5 能够产生多种类型的生物活性化合物。然而，该菌株可能还有合成更多有用次级代谢产物的潜力。在这里，我们使用异源表达激活了弗氏链霉菌 FRI-5 中一个未鉴定化合物的沉默生物合成基因簇。携带沉默基因簇的工程菌株产生了化合物 5，而该化合物在弗氏链霉菌 FRI-5 的发酵液中无法检测到。通过各种光谱分析，我们阐明了化合物 5（命名为 lavendiol）的化学结构，它是一种新的含二醇的聚酮化合物。lavendiol 的建议组装线展示了聚酮化合物的独特生物合成机制。本研究的结果表明，通过基因组挖掘和异源表达，有可能从链霉菌中发现更多的沉默有用化合物。
