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Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.
Xiang, Lang; Shi, Jing; Zhu, Ao; Xu, Zi Fei; Liu, Shuang He; Wang, Yi Shuang; Guo, Zhi Kai; Jiao, Rui Hua; Tan, Ren Xiang; Ge, Hui Ming.
Afiliación
  • Xiang L; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Shi J; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Zhu A; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Xu ZF; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Liu SH; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Wang YS; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Guo ZK; Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, China.
  • Jiao RH; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Tan RX; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • Ge HM; State Key Laboratory of Ph armaceutical Biotechnology, Institute of Functional Biomolecules, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing, 210023, China.
Angew Chem Int Ed Engl ; 62(13): e202218660, 2023 03 20.
Article en En | MEDLINE | ID: mdl-36727486
Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos Biológicos / Policétidos Idioma: En Revista: Angew Chem Int Ed Engl Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos Biológicos / Policétidos Idioma: En Revista: Angew Chem Int Ed Engl Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania