Identification of the Biosynthetic Gene Cluster and Regulatory Cascade for the Synergistic Antibacterial Antibiotics Griseoviridin and Viridogrisein in Streptomyces griseoviridis
其他题名mannual of IR1
Xie, YC; Wang, B; Liu, J; Zhou, JC; Ma, JY; Huang, HB; Ju, JH; jju@scsio.ac.cn
2012
发表期刊CHEMBIOCHEM
ISSN1439-4227
卷号13期号:18页码:2745-2757
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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
部门归属[Xie, Yunchang; Wang, Bo; Liu, Jing; Zhou, Junchao; Ma, Junying; Huang, Hongbo; Ju, Jianhua] Chinese Acad Sci, CAS Key Lab Marine Bioresources Sustainable Utili, Guangdong Key Lab Marine Mat Med, RNAM Ctr Marine Microbiol,S China Sea Inst Oceano, Guangzhou 510301, Guangdong, Peoples R China; [Xie, Yunchang; Liu, Jing; Zhou, Junchao] Chinese Acad Sci, Grad Univ, Beijing 110039, Peoples R China
关键词Antibacterial Biosynthetic Gene Clusters Griseoviridin Regulatory Cascades Streptomyces Griseoviridis Viridogrisein
学科领域Biochemistry & Molecular Biology ; Chemistry, Medicinal
资助者国科图 ; 国科图 ; 国科图 ; 国科图
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收录类别sci
语种英语
资助项目LMB
资助者国科图 ; 国科图 ; 国科图 ; 国科图
WOS记录号WOS:000312546300015
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被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/9726
专题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
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GB/T 7714
Xie, YC,Wang, B,Liu, J,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 Xie, YC.,Wang, B.,Liu, J.,Zhou, JC.,Ma, JY.,...&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 Xie, YC,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.
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