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Identification and characterization of a biosynthetic gene cluster for tryptophan dimers in deep sea-derived Streptomyces sp SCSIO 03032
Ma, L; Zhang, WJ; Zhu, YG; Zhang, GT; Zhang, HB; Zhang, QB; Zhang, LP; Yuan, CS; Zhang, CS; czhang2006@gmail.com
2017
Source PublicationAPPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume101Issue:15Pages:6123-6136
AbstractTryptophan dimers (TDs) are an important class of natural products with diverse bioactivities and share conserved biosynthetic pathways. We report the identification of a partial gene cluster (spm) responsible for the biosynthesis of a class of unusual TDs with non-planar skeletons including spiroindimicins (SPMs), indimicins (IDMs), and lynamicins (LNMs) from the deep-sea derived Streptomyces sp. SCSIO 03032. Bioinformatics analysis, targeted gene disruptions, and heterologous expression studies confirmed the involvement of the spm gene cluster in the biosynthesis of SPM/IDM/LNMs, and revealed the indispensable roles for the halogenase/reductase pair SpmHF, the amino acid oxidase SpmO, and the chromopyrrolic acid (CPA) synthase SpmD, as well as the positive regulator SpmR and the putative transporter SpmA. However, the spm gene cluster was unable to confer a heterologous host the ability to produce SPM/IDM/LNMs. In addition, the P450 enzyme SpmP and the monooxygenase SpmX2 were found to be non-relevant to the biosynthesis of SPM/IDM/LNMs. Sequence alignment and structure modeling suggested the lack of key conserved amino acid residues in the substrate-binding pocket of SpmP. Furthermore, feeding experiments in the non-producing Delta spmO mutant revealed several biosynthetic precursors en route to SPMs, indicating that key enzymes responsible for the biosynthesis of SPMs should be encoded by genes outside of the identified spm gene cluster. Finally, the biosynthetic pathways of SPM/IDM/LNMs are proposed to lay a basis for further insights into their intriguing biosynthetic machinery.
Department[Ma, Liang; Zhang, Wenjun; Zhu, Yiguang; Zhang, Guangtao; Zhang, Haibo; Zhang, Qingbo; Zhang, Liping; Yuan, Chengshan; Zhang, Changsheng] 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; [Ma, Liang] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
KeywordTryptophan Dimers Spiroindimicins Gene Cluster Biosynthesis Heterologous Expression Deep Sea
Funding ProjectLMB
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/16310
Collection中科院海洋生物资源可持续利用重点实验室
Corresponding Authorczhang2006@gmail.com
Recommended Citation
GB/T 7714
Ma, L,Zhang, WJ,Zhu, YG,et al. Identification and characterization of a biosynthetic gene cluster for tryptophan dimers in deep sea-derived Streptomyces sp SCSIO 03032[J]. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,2017,101(15):6123-6136.
APA Ma, L.,Zhang, WJ.,Zhu, YG.,Zhang, GT.,Zhang, HB.,...&czhang2006@gmail.com.(2017).Identification and characterization of a biosynthetic gene cluster for tryptophan dimers in deep sea-derived Streptomyces sp SCSIO 03032.APPLIED MICROBIOLOGY AND BIOTECHNOLOGY,101(15),6123-6136.
MLA Ma, L,et al."Identification and characterization of a biosynthetic gene cluster for tryptophan dimers in deep sea-derived Streptomyces sp SCSIO 03032".APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 101.15(2017):6123-6136.
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