JOM KITA KE POLITEKNIK

Diene Incorporation by a Dehydratase Domain Variant in Modular Polyketide Synthases (Record no. 1842)

MARC details
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100 10 - MAIN ENTRY--PERSONAL NAME
Personal name Hobson, Christian
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9 (RLIN) 1618
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Title Diene Incorporation by a Dehydratase Domain Variant in Modular Polyketide Synthases
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Date of publication, distribution, etc. 2022-12.
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General note /pmc/articles/PMC7613849/
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General note /pubmed/36109649
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Summary, etc. Modular polyketide synthases (PKSs) are biosynthetic assembly lines that construct structurally diverse natural products with wide-ranging applications in medicine and agriculture. Various mechanisms contribute to structural diversification during PKS-mediated chain assembly, including dehydratase (DH) domain-mediated elimination of water from R and S-configured 3-hydroxy thioesters to introduce E and Z-configured carbon-carbon double bonds, respectively. Here we report the discovery of a novel DH domain variant that catalyses the sequential elimination of two molecules of water from a (3R, 5S)-3, 5-dihydroxy thioester during polyketide chain assembly, introducing a - conjugated E, Z-diene into various modular PKS products. We show that the reaction proceeds via a (2E, 5S)-2-enoyl-5-hydroxy thioester intermediate and involves an additional universally conserved histidine residue that is absent from the active site of most conventional DH domains. These findings expand the diverse range of chemistries mediated by DH-like domains in modular PKSs, highlighting the catalytic versatility of the double hot dog fold.
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Terms governing use and reproduction
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Terms governing use and reproduction https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
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Language note en
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Topical term or geographic name as entry element Article
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Genre/form data or focus term Text
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700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Jenner, Matthew
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9 (RLIN) 1619
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Jian, Xinyun
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9 (RLIN) 1620
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Personal name Griffiths, Daniel
Relator term author
9 (RLIN) 1621
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Roberts, Douglas M.
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9 (RLIN) 1622
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Personal name Rey-Carrizo, Matias
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9 (RLIN) 1623
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Challis, Gregory L.
Relator term author
9 (RLIN) 1624
786 0# - DATA SOURCE ENTRY
Note Nat Chem Biol
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1038/s41589-022-01127-y">http://dx.doi.org/10.1038/s41589-022-01127-y</a>
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