Quorum sensing-based metabolic engineering of the precursor supply in Streptomyces coelicolor to improve heterologous production of neoaureothin

Do Kyung Kim, Boncheol Gu, Duck Gyun Kim, Min Kyu Oh

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Streptomyces are important industrial bacteria that produce pharmaceutically valuable polyketides. However, mass production on an industrial scale is limited by low productivity, which can be overcome through metabolic engineering and the synthetic biology of the host strain. Recently, the introduction of an auto-inducible expression system depending on microbial physiological state has been suggested as an important tool for the industrial-scale production of polyketides. In this study, titer improvement by enhancing the pool of CoA-derived precursors required for polyketide production was driven in a quorum sensing (QS)-dependent manner. A self-sustaining and inducer-independent regulatory system, named the QS-based metabolic engineering of precursor pool (QMP) system, was constructed, wherein the expression of genes involved in precursor biosynthesis was regulated by the QS-responsive promoter, scbAp. The QMP system was applied for neoaureothin production in a heterologous host, Streptomyces coelicolor M1152, and productivity increased by up to 4-fold. In particular, the engineered hyperproducers produced high levels of neoaureothin without adversely affecting cell growth. Overall, this study showed that self-regulated metabolic engineering mediated by QS has the potential to engineer strains for polyketide titer improvement.

Original languageEnglish
Pages (from-to)2039-2044
Number of pages6
JournalBiotechnology and Bioengineering
Volume120
Issue number7
DOIs
Publication statusPublished - 2023 Jul

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2018M3A9F3079662, 2020R1A2B5B01002347).

Publisher Copyright:
© 2023 Wiley Periodicals LLC.

Keywords

  • heterologous production
  • metabolic engineering
  • neoaureothin
  • polyketide
  • quorum sensing
  • Streptomyces

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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