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; Li, WL (reprint author), Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ China, Qingdao 266003, Peoples R China.
2016
发表期刊MICROBIAL CELL FACTORIES
卷号15页码:-
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.
部门归属[Huang, Huiming; Hou, Lukuan; Li, Huayue; Qiu, Yanhong; Li, Wenli] Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ China, Qingdao 266003, Peoples R China; [Ju, Jianhua] Chinese Acad Sci, South China Sea Inst Oceanol, RNAM Ctr Marine Microbiol, Guangdong Key Lab Marine Mat Med,CAS Key Lab Mari, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China ; LMB
关键词Deepsea-derived Streptomyces Cryptic Gene Cluster Whib-like (Wbl) Gene Violapyrones (Vlps) Type Iii Polyketide Synthase (Pks)
学科领域Biotechnology & Applied Microbiology
文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/15395
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Li, WL (reprint author), Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ China, Qingdao 266003, Peoples R China.
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, WL .(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):-.
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