title: Improvement of daptomycin production via increased resistance to decanoic acid in Streptomyces roseosporus.
abstract: Daptomycin, a cyclic anionic lipopeptide compound produced by Streptomyces roseosporus, is used to treat skin infections caused by multi-drug resistant gram-positive pathogens. The biosynthesis of daptomycin is initiated by the condensation of decanoic acid (DA, a 10-carbon unit fatty acid) and the N-terminal l-tryptophan. So, the addition of DA to the fermentation medium is essential for increasing daptomycin production. However, increasing of DA concentration in the fermentation medium was not possible due to the high toxicity of DA. The previous studies reported that the cell growth of S. roseosporus was halted from 1 mM DA. In order to improve daptomycin production with increasing DA concentration in the medium, the DA-resistant S. roseosporus was developed via a sequential-adaptation method. The DA-resistant strain (DAR) showed complete resistance to 1 mM DA, and the daptomycin production was increased 1.4-fold (40.5 ± 0.7 mg/L) compared with the wild-type (28.5 ± 0.8 mg/L) at 1 mM DA. Additionally, the initial step of the daptomycin biosynthesis was enhanced by the overexpression of dptE and dptF in DAR. The dptEF overexpression DAR showed 3.9-fold (156.3 ± 8.2 mg/L) increase in the daptomycin production compared with DAR (40.1 ± 2.6 mg/L) at 1 mM DA.
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin 449728, South Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program of Biomodulation, Myongji University, Yongin 449728, South Korea.
authors.forename: Hong Rip
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin 449728, South Korea.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Jin
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin 449728, South Korea; Interdisciplinary Program of Biomodulation, Myongji University, Yongin 449728, South Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin 449728, South Korea. Electronic address: jwsuh@mju.ac.kr.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D019149:Bioreactors; D017576:Daptomycin / Q000096:biosynthesis*; D003652:Decanoic Acids / Q000378:metabolism* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics; D005285:Fermentation / Q000187:drug effects; D013302:Streptomyces / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D003652:Decanoic Acids; C031071:decanoic acid; D014364:Tryptophan; D017576:Daptomycin
keywords: Daptomycin; Decanoic acid; Sequential adaptation; Streptomyces roseosporus; Toxicity