A gamma-butyrolactone-sensing activator/repressor, JadR3, controls a regulatory mini-network for jadomycin biosynthesis----中国科学院微生物研究所

科研成果

论文题目:	A gamma-butyrolactone-sensing activator/repressor, JadR3, controls a regulatory mini-network for jadomycin biosynthesis
作者:	Zou Zhengzhong, Du Deyao, Zhang Yanyan, Zhang Jihui, Niu Guoqing, Tan Huarong
联系作者:	Niu Guoqing, Tan Huarong
刊物名称:	Mol Microbiol
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年份:	2014
影响因子:	5.051
论文下载:	http://onlinelibrary.wiley.com/doi/10.1111/mmi.12752/abstract;jsessionid=0A721CE3B0D1C140D717D36FA040B859.f03t03
摘要:	Two regulatory genes, jadR2 and jadR3, in the jadomycin (jad) biosynthetic gene cluster of Streptomyces venezuelae encode homologues of gamma-butyrolactone receptor. JadR2 was previously shown to be a pseudo gamma-butyrolactone receptor. jadR3 is situated at the upstream of jadW123 encoding putative enzymes for gamma-butyrolactone biosynthesis. Disruption of jadR3 resulted in markedly decreased production of jadomycin. Transcriptional analysis revealed that JadR3 represses jadW1, jadR2 and jadR3 but activates jadR1, the key activator gene for jadomycin biosynthesis. DNase I footprinting showed that JadR3 has four binding sites in the intergenic regions of jadR2-jadR1 and jadR3-jadW1. A JadR3 interactive molecule, SVB1, was purified from a large-scale fermentation and its structure found to be the same as SCB3, a gamma-butyrolactone from Streptomyces coelicolor, and was absent from a jadW123 mutant lacking jadomycin production. Addition of SVB1 or extract from S. coelicolor to the mutant restored jadomycin production. Overall, our results revealed that the association of JadR3 and SVB1 plays an important role in controlling a regulatory mini-network governing jadomycin biosynthesis, providing new insights into the ways in which gamma-butyrolactone/receptor systems modulate antibiotic biosynthesis in Streptomyces.