Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis

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	Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis
	Ma, JY; Xie, YC; Wang, B; Liu, J; Zhou, JC; Huang, HB; Ju, JH; jju@scsio.ac.cn
刊名	CHEMBIOCHEM
	2012
卷号	13 期号:18 页码:2745-2757
关键词	Antibacterial Biosynthetic Gene Clusters Griseoviridin Regulatory Cascades Streptomyces Griseoviridis Viridogrisein
ISSN号	1439-4227
其他题名	mannual of IR1
产权排序	产权排序
英文摘要	Griseoviridin (GV) and viridogrisein (VG, also referred to as etamycin), produced by Streptomyces griseoviridis, are two chemically unrelated compounds belonging to the streptogramin family. Both of these natural products demonstrate broad-spectrum antibacterial activity and constitute excellent candidates for future drug development. To elucidate the biosynthetic machinery associated with production of these two unique antibiotics, the gene cluster responsible for both GV and VG production was identified within the Streptomyces griseoviridis genome and characterized, and its function in GV and VG biosynthesis was confirmed by inactivation of 30 genes and complementation experiments. This sgv gene cluster is localized to a 105 kb DNA region that consists of 36 open reading frames (ORFs), including four nonribosomal peptide synthetases (NRPSs) for VG biosynthesis and a set of hybrid polyketide synthases (PKS)-NRPSs with a discrete acyltransferase (AT), SgvQ, to assemble the GV backbone. The enzyme encoding genes for VG versus GV biosynthesis are separated into distinct halves of the cluster. A series of four genes: sgvA, sgvB, sgvC, and sgvK, were found downstream of the PKS-NRPS; these likely code for construction of a ?-butyrolactone (GBL)-like molecule. GBLs and the corresponding GBL receptor systems are the highest ranked regulators that are able to coordinate the two streptomyces antibiotic regulatory protein (SARP) family positive regulators SgvR2 and SgvR3; both are key biosynthetic activators. Models of GV, VG, and GBL biosynthesis were proposed by using functional gene assignments, determined on the basis of bioinformatics analysis and further supported by in vivo gene inactivation experiments. Overall, this work provides new insights into the biosyntheses of the GV and VG streptogramins that are potentially applicable to a host of combinatorial biosynthetic scenarios.; description.abstract
学科主题	Biochemistry & Molecular Biology ; Chemistry, Medicinal
URL标识	查看原文
资助项目	LMB
语种	英语
WOS记录号	WOS:000312546300015
资助机构	国科图 ; 国科图 ; 国科图 ; 国科图
公开日期	2013-08-28
内容类型	期刊论文
源URL	[http://ir.scsio.ac.cn/handle/344004/9726]
专题	南海海洋研究所_中科院海洋生物资源可持续利用重点实验室
通讯作者	jju@scsio.ac.cn
推荐引用方式 GB/T 7714	Ma, JY,Xie, YC,Wang, B,et al. Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis[J]. CHEMBIOCHEM,2012,13(18):2745-2757.
APA	Ma, JY.,Xie, YC.,Wang, B.,Liu, J.,Zhou, JC.,...&jju@scsio.ac.cn.(2012).Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis.CHEMBIOCHEM,13(18),2745-2757.
MLA	Ma, JY,et al."Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis".CHEMBIOCHEM 13.18(2012):2745-2757.