Activation of a plasmid-situated type III PKS gene cluster by deletion of a wbl gene in deepsea-derived Streptomyces somaliensis SCSIO ZH66

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	Activation of a plasmid-situated type III PKS gene cluster by deletion of a wbl gene in deepsea-derived Streptomyces somaliensis SCSIO ZH66
	Huang, Huiming; Hou, Lukuan; Li, Huayue; Qiu, Yanhong; Ju, Jianhua; Li, Wenli
刊名	MICROBIAL CELL FACTORIES
	2016
卷号	15 页码:-
关键词	Deepsea-derived Streptomyces Cryptic gene cluster whiB-like (wbl) gene Violapyrones (VLPs) Type III polyketide synthase (PKS)
通讯作者	Li, WL (reprint author), Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ China, Qingdao 266003, Peoples R China.
中文摘要	Background: Actinomycete genome sequencing has disclosed a large number of cryptic secondary metabolite bio-synthetic gene clusters. However, their unavailable or limited expression severely hampered the discovery of bioactive compounds. The whiB-like (wbl) regulatory genes play important roles in morphological differentiation as well as secondary metabolism; and hence the wblA(so) gene was probed and set as the target to activate cryptic gene clusters in deepsea-derived Streptomyces somaliensis SCSIO ZH66. Results: wblA(so) from deepsea-derived S. somaliensis SCSIO ZH66 was inactivated, leading to significant changes of secondary metabolites production in the Delta wblA(so) mutant, from which a-pyrone compound violapyrone B (VLP B) was isolated. Subsequently, the VLP biosynthetic gene cluster was identified and characterized, which consists of a type III polyketide synthase (PKS) gene vioA and a regulatory gene vioB; delightedly, inactivation of vioB led to isolation of another four VLPs analogues, among which one was new and two exhibited improved anti-MRSA (methicillin-resistant Staphylococcus aureus, MRSA) activity than VLP B. Moreover, transcriptional analysis revealed that the expression levels of whi genes (whiD, whiG, whiH and whiI) and wbl genes (wblC, wblE, wblH, wblI and wblK) were repressed by different degrees, suggesting an intertwined regulation mechanism of wblA(so) in morphological differentiation and secondary metabolism of S. somaliensis SCSIO ZH66. Conclusions: wblA orthologues would be effective targets for activation of cryptic gene clusters in marine-derived Streptomyces strains, notwithstanding the regulation mechanisms might be varied in different strains. Moreover, the availability of the vio gene cluster has enriched the diversity of type III PKSs, providing new opportunities to expand the chemical space of polyketides through biosynthetic engineering.
学科主题	Biotechnology & Applied Microbiology
内容类型	期刊论文
源URL	[http://ir.scsio.ac.cn/handle/344004/15395]
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
推荐引用方式 GB/T 7714	Huang, Huiming,Hou, Lukuan,Li, Huayue,et al. Activation of a plasmid-situated type III PKS gene cluster by deletion of a wbl gene in deepsea-derived Streptomyces somaliensis SCSIO ZH66[J]. MICROBIAL CELL FACTORIES,2016,15:-.
APA	Huang, Huiming,Hou, Lukuan,Li, Huayue,Qiu, Yanhong,Ju, Jianhua,&Li, Wenli.(2016).Activation of a plasmid-situated type III PKS gene cluster by deletion of a wbl gene in deepsea-derived Streptomyces somaliensis SCSIO ZH66.MICROBIAL CELL FACTORIES,15,-.
MLA	Huang, Huiming,et al."Activation of a plasmid-situated type III PKS gene cluster by deletion of a wbl gene in deepsea-derived Streptomyces somaliensis SCSIO ZH66".MICROBIAL CELL FACTORIES 15(2016):-.