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Transcriptome analysis of wild-type and afsS deletion mutant strains identifies synergistic transcriptional regulator of afsS for a high antibiotic-producing strain of Streptomyces coelicolor A3(2)

Title
Transcriptome analysis of wild-type and afsS deletion mutant strains identifies synergistic transcriptional regulator of afsS for a high antibiotic-producing strain of Streptomyces coelicolor A3(2)
Authors
Kim, M.W.Lee, B.-R.You, S.Kim, E.-J.Kim, J.-N.Song, E.Yang, Y.-H.Hwang, Dae HeeKim, B.-G.
DGIST Authors
Hwang, Dae Hee
Issue Date
2018-04
Citation
Applied Microbiology and Biotechnology, 102(7), 3243-3253
Type
Article
Article Type
Article
Keywords
AntibioticsBacteriaBiochemistryBiosynthesisMetabolismActinorhodinClustering analysisStreptomyces coelicolorTranscriptional regulatorTranscriptomesTime series analysis
ISSN
0175-7598
Abstract
Most secondary metabolism in Actinobacteria is controlled by multi-layered, gene-regulatory networks. These regulatory mechanisms are not easily identified due to their complexity. As a result, when a strong transcriptional regulator (TR) governs activation of biosynthetic pathways of target antibiotics such as actinorhodin (ACT), additional enhancement of the biosynthesis is difficult in combination with other TRs. To find out any “synergistic transcriptional regulators (sTRs)” that show an additive effect on the major, often strong, transcriptional regulator (mTR), here, we performed a clustering analysis using the transcriptome datasets of an mTR deletion mutant and wild-type strain. In the case of ACT biosynthesis in Streptomyces coelicolor, PhoU (SCO4228) and RsfA (SCO4677) were selected through the clustering analysis, using AfsS (SCO4425) as a model mTR, and experimentally validated their roles as sTRs. Furthermore, through analysis of synergistic effects, we were able to suggest a novel regulation mechanism and formulate a strategy to maximize the synergistic effect. In the case of the double TR mutant strain (ΔrsfA pIBR25::afsS), it was confirmed that the increase of cell mass was the major cause of the synergistic effect. Therefore, the strategy to increase the cell mass of double mutant was further attempted by optimizing the expression of efflux pump, which resulted in 2-fold increase in the cell mass and 24-fold increase in the production of ACT. This result is the highest ACT yield from S. coelicolor ever reported. © 2018 Springer-Verlag GmbH Germany, part of Springer Nature
URI
http://hdl.handle.net/20.500.11750/5924
DOI
10.1007/s00253-018-8838-3
Publisher
Springer Verlag
Related Researcher
  • Author Hwang, Daehee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
Department of New BiologySystems Biology and Medicine Lab1. Journal Articles


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