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Enhancement of himastatin bioproduction via inactivation of atypical repressors in Streptomyces hygroscopicus.
Xie, Yunchang; Li, Qinglian; Qin, Xiangjing; Ju, Jianhua; Ma, Junying.
Affiliation
  • Xie Y; CAS Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Network for Applied Microbiology Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • Li Q; CAS Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Network for Applied Microbiology Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • Qin X; CAS Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Network for Applied Microbiology Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • Ju J; CAS Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Network for Applied Microbiology Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • Ma J; College of Earth Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Metab Eng Commun ; 8: e00084, 2019 Jun.
Article de En | MEDLINE | ID: mdl-30671346
Three atypical regulatory genes, hmtABD have been discovered within the himastatin biosynthetic gene cluster (BGC) in Streptomyces hygroscopicus ATCC 53653 and the roles of their products have been identified. HmtA and HmtD do not show any structurally distinct features characteristic of regulatory function yet were shown to play important repressive and stimulatory roles, respectively, related to himastatin biosynthesis. HmtB encodes a conserved acetylglutamate kinase; new member of this family serves as repressor of secondary metabolism. Through repressive networks engineering, the limiting functions of HmtA and HmtB along with the activating functions of HmtD in the himastatin BGC have been identified for the first time by gene activation, qPCR, RT-PCR and HPLC studies of selected mutant strains; two of these mutant strains (ΔhmtA and ΔhmtB) produced himastatin in titers (19.02 ±â€¯1.2 µg/mL, 9.9 folds and 30.40 ±â€¯0.83 µg/mL, 15.8 folds) far exceeding those of the wild-type (WT) producer. Overall, this work provides significant insight into secondary metabolic regulatory mechanisms in Streptomyces. These efforts also highlight and validate a new strategy enabling expanded exploitation of cyclopeptidic natural products such as himastatin that demonstrate exciting antimicrobial and antitumor potentials.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Type d'étude: Prognostic_studies Langue: En Journal: Metab Eng Commun Année: 2019 Type de document: Article Pays d'affiliation: Chine Pays de publication: Pays-Bas

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Type d'étude: Prognostic_studies Langue: En Journal: Metab Eng Commun Année: 2019 Type de document: Article Pays d'affiliation: Chine Pays de publication: Pays-Bas