title: Multiple transporters are involved in natamycin efflux in Streptomyces chattanoogensis L10.
abstract: Antibiotic-producing microorganisms have evolved several self-resistance mechanisms to prevent auto-toxicity. Overexpression of specific transporters to improve the efflux of toxic antibiotics has been found one of the most important and intrinsic resistance strategies used by many Streptomyces strains. In this work, two ATP-binding cassette (ABC) transporter-encoding genes located in the natamycin biosynthetic gene cluster, scnA and scnB, were identified as the primary exporter genes for natamycin efflux in Streptomyces chattanoogensis L10. Two other transporters located outside the cluster, a major facilitator superfamily transporter Mfs1 and an ABC transporter NepI/II were found to play a complementary role in natamycin efflux. ScnA/ScnB and Mfs1 also participate in exporting the immediate precursor of natamycin, 4,5-de-epoxynatamycin, which is more toxic to S. chattanoogensis L10 than natamycin. As the major complementary exporter for natamycin efflux, Mfs1 is up-regulated in response to intracellular accumulation of natamycin and 4,5-de-epoxynatamycin, suggesting a key role in the stress response for self-resistance. This article discusses a novel antibiotic-related efflux and response system in Streptomyces, as well as a self-resistance mechanism in antibiotic-producing strains.
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Tan-Jun
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shan
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Wei-Wang
authors.initials: WW
authors.lastname: Dou
authors.affiliation: College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Xin-Hang
authors.initials: XH
authors.lastname: Jiang
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.|Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolism Engineering, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Mao
authors.affiliation: College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Liu
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.|Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolism Engineering, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Guan
authors.affiliation: Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.|Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolism Engineering, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Li
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001692:Biological Transport / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics* / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D010866:Natamycin / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D010866:Natamycin