Restoration of a bioactive lantibiotic suicin from a remnant lan locus of pathogenic Streptococcus suis serotype 2----中国科学院微生物研究所

科研成果

论文题目:	Restoration of a bioactive lantibiotic suicin from a remnant lan locus of pathogenic Streptococcus suis serotype 2
作者:	Wang Jian, Gao Yong, Teng Kunling, Zhang Jie, Sun Shutao, Zhong Jin*
联系作者:	Zhong Jin*
刊物名称:	Appl Environ Microbiol
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年份:	2013
影响因子:	4.406
论文下载:	http://aem.asm.org/content/early/2013/11/18/AEM.03213-13.long
摘要:	Lantibiotics are ribosomally-synthesized, posttranslationally modified antimicrobial peptides. Their biosynthesis genes are usually organized in gene clusters, which are mainly found in Gram-positive bacteria including pathogenic streptococci. Three highly virulent Streptococcus suis serotype 2 strains (98HAH33, 05ZYH33 and SC84) have been identified to contain a 89K pathogenicity island. Here, on these islands, we unveiled and re-annotated a putative lantibiotic locus designated sui which contains a virulence-associated two component regulator suiK/suiR. In silico analysis revealed that the putative lantibiotic modification gene suiM was interrupted by a 7.9 kb integron and other biosynthesis-related genes contained various frame-shift mutations. By reconstituting the intact suiM in Escherichia coli together with a semi-in vitro biosynthesis system, a putative lantibiotic named suicin was produced with bactericidal activities against a variety of Gram-positive strains including pathogenic streptococci and vancomycin-resistant enterococci. Ring topology dissection indicated that the 34-amino-acid lantibiotic contained two methyllanthionine residues and one disulfide bridge, which render suicin in an N-terminal linear and C-terminal globular shape. To confirm the function of suiK/suiR, SuiR was overexpressed and purified. In vitro analysis showed that SuiR could specifically bind to suiA gene promoter. Its co-expression of with suiK could activate suiA gene promoter in Lactococcus lactis NZ9000. Conclusively, we obtained a novel lantibiotic suicin by restoring its production from the remnant sui locus and demonstrated that the virulence-associated SuiK/SuiR regulates its production.