Improvement of gougerotin and nikkomycin production by engineering their biosynthetic gene clusters----中国科学院微生物研究所

科研成果

论文题目:	Improvement of gougerotin and nikkomycin production by engineering their biosynthetic gene clusters
作者:	Du Deyao, Zhu Yu, Wei Junhong, Tian Yuqing, Niu Guoqing, Tan Huarong
联系作者:	Niu Guoqing, Tan Huarong
刊物名称:	Applied microbiology and biotechnology
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年份:	2013
影响因子:	3.613
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摘要:	Nikkomycins and gougerotin are peptidyl nucleoside antibiotics with broad biological activities. The nikkomycin biosynthetic gene cluster comprises one pathway-specific regulatory gene (sanG) and 21 structural genes, whereas the gene cluster for gougerotin biosynthesis includes one putative regulatory gene, one major facilitator superfamily transporter gene, and 13 structural genes. In the present study, we introduced sanG driven by six different promoters into Streptomyces ansochromogenes TH322. Nikkomycin production was increased significantly with the highest increase in engineered strain harboring hrdB promoter-driven sanG. In the meantime, we replaced the native promoter of key structural genes in the gougerotin (gou) gene cluster with the hrdB promoters. The heterologous producer Streptomyces coelicolor M1146 harboring the modified gene cluster produced gougerotin up to 10-fold more than strains carrying the unmodified cluster. Therefore, genetic manipulations of genes involved in antibiotics biosynthesis with the constitutive hrdB promoter present a robust, easy-to-use system generally useful for the improvement of antibiotics production in Streptomyces.