Improvement of daptomycin production via increased resistance to decanoic acid in Streptomyces roseosporus

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of bioscience and bioengineering 2016-10, Vol.122 (4), p.427-433
Main Authors: Lee, Sung-Kwon, Kim, Hong Rip, Jin, Ying-Yu, Yang, Seung Hwan, Suh, Joo-Won
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - biosynthesis
Bioreactors
Daptomycin
Daptomycin - biosynthesis
Decanoic acid
Decanoic Acids - metabolism
Decanoic Acids - pharmacology
Drug Resistance, Bacterial - drug effects
Drug Resistance, Bacterial - genetics
Fermentation - drug effects
Sequential adaptation
Streptomyces - drug effects
Streptomyces - genetics
Streptomyces - growth & development
Streptomyces - metabolism
Streptomyces roseosporus
Toxicity
Tryptophan - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1389-1723
1347-4421
DOI:10.1016/j.jbiosc.2016.03.026