Identification and characterization of wblA-dependent tmcT regulation during tautomycetin biosynthesis in Streptomyces sp CK4412
- Authors
- Nah, Ji-Hye; Park, Shin-Hae; Yoon, Hye-Mi; Choi, Si-Sun; Lee, Chul-Hoon; Kim, Eung-Soo
- Issue Date
- Jan-2012
- Publisher
- Elsevier BV
- Keywords
- Streptomyces; Tautomycetin; wblA; tmcT; Immunosuppressant
- Citation
- Biotechnology Advances, v.30, no.1, pp 202 - 209
- Pages
- 8
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Biotechnology Advances
- Volume
- 30
- Number
- 1
- Start Page
- 202
- End Page
- 209
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/33924
- DOI
- 10.1016/j.biotechadv.2011.05.004
- ISSN
- 0734-9750
1873-1899
- Abstract
- Tautomycetin (TMC) is an unusual linear polyketide compound esterified with a cyclic anhydride. It exhibits novel activated T cell-specific immunosuppressant as well as anti-cancer activities. Previously, we isolated and characterized the entire TMC biosynthetic gene cluster from Streptomyces sp. CK4412, including a TMC pathway-specific gene, tmcN, the over-expression of which led to a significant increase in TMC productivity. In addition, we also reported that WblA acts as a global down-regulator of antibiotic biosynthesis through pathway-specific regulation in Streptomyces species. Here, we confirm that TmcT acts as another TMC pathway-specific regulator within the TMC biosynthetic cluster. Specifically, tmcT deletion resulted in the complete loss of TMC production, whereas complementation with a tmcT-carrying integrative plasmid significantly restored TMC biosynthesis. We also identified a 0.39 kb wblA ortholog (named wblA(tmc)) from Streptomyces sp. CK4412 via genomic DNA library screening that showed 96% amino acid identity compared to a previously-known S. coelicolor wblA. Targeted gene disruption of wblA(tmc) in Streptomyces sp. CK4412 exhibited approximately 3-fold higher TMC productivity than that in the wild-type strain. Moreover, transcription analyses of the TMC biosynthetic and regulatory genes revealed that the expression of tmcT was strongly down-regulated by wblA(tmc). These results imply that the TMC biosynthetic regulation network is controlled by two pathway-specific positive regulator, WblA(tmc)-dependent TmcT as well as WblA(tmc)-independent TmcN in Streptomyces sp. CK4412. (C) 2011 Elsevier Inc. All rights reserved.
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