| 000 | 02318 am a22002773u 4500 | ||
|---|---|---|---|
| 042 | _adc | ||
| 100 | 1 | 0 |
_aHobson, Christian _eauthor _91618 |
| 700 | 1 | 0 |
_aJenner, Matthew _eauthor _91619 |
| 700 | 1 | 0 |
_aJian, Xinyun _eauthor _91620 |
| 700 | 1 | 0 |
_aGriffiths, Daniel _eauthor _91621 |
| 700 | 1 | 0 |
_aRoberts, Douglas M. _eauthor _91622 |
| 700 | 1 | 0 |
_aRey-Carrizo, Matias _eauthor _91623 |
| 700 | 1 | 0 |
_aChallis, Gregory L. _eauthor _91624 |
| 245 | 0 | 0 | _aDiene Incorporation by a Dehydratase Domain Variant in Modular Polyketide Synthases |
| 260 | _c2022-12. | ||
| 500 | _a/pmc/articles/PMC7613849/ | ||
| 500 | _a/pubmed/36109649 | ||
| 520 | _aModular 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. | ||
| 540 | _a | ||
| 540 | _ahttps://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 | ||
| 546 | _aen | ||
| 690 | _aArticle | ||
| 655 | 7 |
_aText _2local |
|
| 786 | 0 | _nNat Chem Biol | |
| 856 | 4 | 1 |
_uhttp://dx.doi.org/10.1038/s41589-022-01127-y _zConnect to this object online. |
| 999 |
_c819 _d819 |
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