Journal
MICROBIAL CELL FACTORIES
Volume 12, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1475-2859-12-19
Keywords
Daptomycin; Decanoic acid; Toxic; Tolerance; Streptomyces roseosporus
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Funding
- National Natural Science Foundation of China [31100069]
- Natural Science Foundation Project of CQ CSTC [cstc2012jjA10149]
- Fundamental Research Funds for the Central Universities [XDJK2013A010]
- New Century Excellent Talents in Universities [NCET-11-0703]
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Backgroud: Daptomycin is an important antibiotic against infections caused by drug-resistant pathogens. Its production critically depends on the addition of decanoic acid during fermentation. Unfortunately, decanoic acid (>2.5 mM) is toxic to daptomycin producer, Streptomyces roseosporus. Results: To understand the mechanism underlying decanoic tolerance or toxicity, the responses of S. roseosporus was determined by a combination of phospholipid fatty acid analysis, reactive oxygen species (ROS) measurement and RNA sequencing. Assays using fluorescent dyes indicated a sharp increase in reactive oxygen species during decanoic acid stress; fatty acid analysis revealed a marked increase in the composition of branched-chain fatty acids by approximately 10%, with a corresponding decrease in straight-chain fatty acids; functional analysis indicated decanoic acid stress has components common to other stress response, including perturbation of respiratory functions (nuo and cyd operons), oxidative stress, and heat shock. Interestingly, our transcriptomic analysis revealed that genes coding for components of proteasome and related to treholase synthesis were up-regulated in the decanoic acid -treated cells. Conclusion: These findings represent an important first step in understanding mechanism of decanoic acid toxicity and provide a basis for engineering microbial tolerance.
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