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Diisonitrile Natural Product SF2768 Functions As a Chalkophore That Mediates Copper Acquisition in Streptomyces thioluteus
Wang, LJ; Zhu, MY; Zhang, QB; Zhang, X; Yang, PL; Liu, ZH; Deng, Y; Zhu, YG; Huang, XS; Han, L; Li, SQ; He, J; hejingjj@mail.hzau.edu.cn
2018
Source PublicationACS CHEMICAL BIOLOGY
Volume12Issue:12Pages:3067-3075
AbstractA nonribosomal peptide synthetase (NRPS) gene duster (sfa) was identified in Streptomyces thioluteus to direct the biosynthesis of the diisonitrile antibiotic SF2768. Its biosynthetic pathway was reasonably proposed based on bioinformatics analysis, metabolic profiles of mutants, and the elucidation of the intermediate and shunt product structures. Bioinformatics-based alignment found a putative ATP-binding cassette (ABC) transporter related to iron import within the biosynthetic gene: cluster, which implied that the product might be a siderophore. However, characterization of the metal-binding properties by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), metal-ligand titration, thin-layer chromatography (TLC), and chrome azurol S (CAS) assays revealed that the final product SF2768 and its diisonitrile derivatives specifically bind :topper, rather than iron, to forth. stable complexes. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that the intracellular cupric content of S. thioluteus significantly increased upon incubation with the copper-SF2768 complex, direct evidence for the copper, acquisition function of SF2768. Further in vivo functional characterization of the transport elements for the copper-SF2768 complexes not only confirmed the chalkophore identity of the compound but also gave initial clues into the copper uptake mechanism of this nonmethanotrophic microorganism.
Department[Wang, Lijuan; Zhu, Mengyi; Zhang, Xu; Yang, Panlei; Deng, Yun; He, Jing] Huazhong Agr Univ, Natl Key Lab Agr Microbiol, Coll Life Sci & Technol, Wuhan 430070, Hubei, Peoples R China; [Zhang, Qjngbo; Zhu, Yiguang] Chinese Acad Sci, CAS Key Lab Trop Marine Bioresources & Ecol, RNAM Ctr Marine Microbiol, Guangdong Key Lab Marine Mat Med,South China Sea, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China; [Liu, Zihui; Li, Shengqing] Huazhong Agr Univ, Coll Sci, State Key Lab Agr Microbiol, Wuhan 430070, Hubei, Peoples R China; [Huang, Xueshi; Han, Li] Northeastern Univ, Inst Microbial Pharmaceut, Coll Life & Hlth Sci, Shenyang 110819, Liaoning, Peoples R China
Subject AreaBiochemistry & Molecular Biology
Funding ProjectLMB
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/17044
Collection中科院海洋生物资源可持续利用重点实验室
Corresponding Authorhejingjj@mail.hzau.edu.cn
Recommended Citation
GB/T 7714
Wang, LJ,Zhu, MY,Zhang, QB,et al. Diisonitrile Natural Product SF2768 Functions As a Chalkophore That Mediates Copper Acquisition in Streptomyces thioluteus[J]. ACS CHEMICAL BIOLOGY,2018,12(12):3067-3075.
APA Wang, LJ.,Zhu, MY.,Zhang, QB.,Zhang, X.,Yang, PL.,...&hejingjj@mail.hzau.edu.cn.(2018).Diisonitrile Natural Product SF2768 Functions As a Chalkophore That Mediates Copper Acquisition in Streptomyces thioluteus.ACS CHEMICAL BIOLOGY,12(12),3067-3075.
MLA Wang, LJ,et al."Diisonitrile Natural Product SF2768 Functions As a Chalkophore That Mediates Copper Acquisition in Streptomyces thioluteus".ACS CHEMICAL BIOLOGY 12.12(2018):3067-3075.
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