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Identification of nocamycin biosynthetic gene cluster from Saccharothrix syringae NRRL B-16468 and generation of new nocamycin derivatives by manipulating gene cluster
Mo, XH; Shi, CR; Gui, C; Zhang, YJ; Ju, JH; Wang, QJ; xhmo2013@163.com; qingjiwang2016@hotmail.com
2017
Source PublicationMICROBIAL CELL FACTORIES
Volume16Pages:100-
AbstractBackground: Nocamycins I and II, produced by the rare actinomycete Saccharothrix syringae, belong to the tetramic acid family natural products. Nocamycins show potent antimicrobial activity and they hold great potential for antibacterial agent design. However, up to now, little is known about the exact biosynthetic mechanism of nocamycin. Results: In this report, we identified the gene cluster responsible for nocamycin biosynthesis from S. syringae and generated new nocamycin derivatives by manipulating its gene cluster. The biosynthetic gene cluster for nocamycin contains a 61 kb DNA locus, consisting of 21 open reading frames (ORFs). Five type I polyketide synthases (NcmAI, NcmAII, NcmAIII, NcmAIV, NcmAV) and a non-ribosomal peptide synthetase (NcmB) are proposed to be involved in synthesis of the backbone structure, a Dieckmann cyclase NcmC catalyze the releasing of linear chain and the formation of tetramic acid moiety, five enzymes (NcmEDGOP) are related to post-tailoring steps, and five enzymes (NcmNJKIM) function as regulators. Targeted inactivation of ncmB led to nocamycin production being completely abolished, which demonstrates that this gene cluster is involved in nocamycin biosynthesis. To generate new nocamycin derivatives, the gene ncmG, encoding for a cytochrome P450 oxidase, was inactivated. Two new nocamycin derivatives nocamycin III and nocamycin IV were isolated from the ncmG deletion mutant strain and their structures were elucidated by spectroscopic data analyses. Based on bioinformatics analysis and new derivatives isolated from gene inactivation mutant strains, a biosynthetic pathway of nocamycins was proposed. Conclusion: These findings provide the basis for further understanding of nocamycin biosynthetic mechanism, and set the stage to rationally engineer new nocamycin derivatives via combinatorial biosynthesis strategy.
Department[Mo, Xuhua; Shi, Chunrong; Zhang, Yanjiao; Wang, Qingji] Qingdao Agr Univ, Sch Life Sci, Shandong Key Lab Appl Mycol, Qingdao 266109, Peoples R China; [Gui, Chun; Ju, Jianhua] Chinese Acad Sci, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, RNAM Ctr Marine Microbiol,South China Sea Inst Oc, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China
KeywordNocamycins Biosynthetic Gene Cluster Cytochrome P450 Oxidase Post-tailoring Modification Saccharothrix Syringae
Funding ProjectLMB
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/16298
Collection中科院海洋生物资源可持续利用重点实验室
Corresponding Authorxhmo2013@163.com; qingjiwang2016@hotmail.com
Recommended Citation
GB/T 7714
Mo, XH,Shi, CR,Gui, C,et al. Identification of nocamycin biosynthetic gene cluster from Saccharothrix syringae NRRL B-16468 and generation of new nocamycin derivatives by manipulating gene cluster[J]. MICROBIAL CELL FACTORIES,2017,16:100-.
APA Mo, XH.,Shi, CR.,Gui, C.,Zhang, YJ.,Ju, JH.,...&qingjiwang2016@hotmail.com.(2017).Identification of nocamycin biosynthetic gene cluster from Saccharothrix syringae NRRL B-16468 and generation of new nocamycin derivatives by manipulating gene cluster.MICROBIAL CELL FACTORIES,16,100-.
MLA Mo, XH,et al."Identification of nocamycin biosynthetic gene cluster from Saccharothrix syringae NRRL B-16468 and generation of new nocamycin derivatives by manipulating gene cluster".MICROBIAL CELL FACTORIES 16(2017):100-.
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