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Novel fungal diphenyl ether biosynthetic gene clusters encode a promiscuous oxidase for elevated antibacterial activities.
Liu, Qingpei; Gao, Shuaibiao; Fang, Jin; Gong, Yifu; Zheng, Yiling; Xu, Yao; Zhang, Dan; Wei, Jiayuan; Liao, Liangxiu; Yao, Ming; Wang, Wenjing; Han, Xiaole; Chen, Fusheng; Molnár, István; Yang, Xiaolong.
Afiliación
  • Liu Q; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Gao S; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Fang J; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Gong Y; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Zheng Y; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Xu Y; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Zhang D; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Wei J; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Liao L; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Yao M; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Wang W; School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074 P.R. China 2019001@mail.scuec.edu.cn.
  • Han X; School of Chemistry and Materials Science, South-Central Minzu University Wuhan 430074 P.R. China.
  • Chen F; School of Life Sciences, Guizhou Normal University Guiyang 550025 P.R. China.
  • Molnár I; College of Food Science and Technology, Huazhong Agricultural University Wuhan 430070 P.R. China.
  • Yang X; VTT Technical Research Centre of Finland FI-02044 VTT Espoo Finland istvan.molnar@vtt.fi.
Chem Sci ; 2024 Jul 29.
Article en En | MEDLINE | ID: mdl-39144458
ABSTRACT
Diphenyl ethers (DPEs) are produced by filamentous fungi using polyketide synthases (PKSs) directly, or via Cu oxidase-catalyzed oxidative rearrangements of benzophenone intermediates. Here, we use heterologous expression to reveal a third route towards DPEs in Preussia isomera that relies on an oxidative multienzyme cascade to convert a PKS-generated, ester-linked didepside to depsidones and further to DPEs, and apply comparative genomics to identify conserved biosynthetic gene clusters for this pathway in multiple fungi. The distribution of DPE products is modulated by the expression chassis upon pathway reconstitution. Among the post-PKS enzymes, the DpeH tyrosinase shows considerable substrate promiscuity towards synthetic DPE analogues. By creating hybrid enzymes with a DpeH orthologue from Aspergillus nidulans, we identify the C-terminal region of DpeH to alter substrate recognition. Our work highlights an evolutionarily conserved way to produce DPEs, and provides enzymatic tools to generate DPE analogues with broad spectrum antibiotic activity against multidrug-resistant human pathogens.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Sci Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Sci Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido