基因组挖掘和沉默的 PKS/NRPS 基因簇的激活指导 Totopotensamides 的产生。
Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides.
机构信息
Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences , 164 West Xingang Road, Guangzhou 510301, China.
出版信息
Org Lett. 2017 Oct 20;19(20):5697-5700. doi: 10.1021/acs.orglett.7b02878. Epub 2017 Oct 11.
A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating the regulatory genes, including the knockout of two negative regulators (totR5 and totR3) and overexpression of a positive regulator totR1, to direct the production of the known totopotensamides (TPMs) A (1) and B (3) and a novel sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation of TPM B (3) lacking the glycosyl moiety, which indicated TotG as a dedicated glycosyltransferase in the biosynthesis of 1 and 2.
海洋来源的链霉菌 SCSIO 02999 中的一个 92kb 沉默的杂合聚酮和非核糖体肽基因簇，通过遗传操作调节基因（包括敲除两个负调控基因 totR5 和 totR3 以及过表达一个正调控基因 totR1）被激活，以指导已知的托普托彭酰胺（TPMs）A（1）和 B（3）和一个新的含磺酸基的类似物 TPM C（2）的产生。TotG 的失活导致缺乏糖基部分的 TPM B（3）的积累，这表明 TotG 是 1 和 2 生物合成中的一种专用糖基转移酶。
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