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A fungal ketoreductase domain that displays substrate-dependent stereospecificity

Iterative highly-reducing polyketide synthases (HR-PKSs) from filamentous fungi are the most complex and enigmatic type of PKS discovered to date. Here we uncover an unusual level of programming by the hypothemycin HR-PKS, in which a single ketoreductase domain displays stereospecificity that is con...

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Detalles Bibliográficos
Autores principales: Zhou, Hui, Gao, Zhizeng, Qiao, Kangjian, Wang, Jingjing, Vederas, John C., Tang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307869/
https://www.ncbi.nlm.nih.gov/pubmed/22406519
http://dx.doi.org/10.1038/nchembio.912
Descripción
Sumario:Iterative highly-reducing polyketide synthases (HR-PKSs) from filamentous fungi are the most complex and enigmatic type of PKS discovered to date. Here we uncover an unusual level of programming by the hypothemycin HR-PKS, in which a single ketoreductase domain displays stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed the biosynthesis of an unnatural diastereomer of the natural product dehydrozearalenol.