The Library
A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis
Tools
Tools
Tools
Masschelein, Joleen, Sydor, Paulina K., Hobson, Christian, Howe, Rhiannon, Jones, Cerith, Roberts, Douglas M., Zhong, Ling Yap, Parkhill, Julian, Mahenthiralingam, Eshwar and Challis, Gregory L. (2019) A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis. Nature Chemistry, 11 . 906-912 . doi:10.1038/s41557-019-0309-7
|
PDF
WRAP-dual-transacylation-mechanism-polyketide-synthase-chain-release-enacyloxin-antibiotic-biosynthesis-Challis-2019.pdf - Accepted Version - Requires a PDF viewer. Download (1327Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/s41557-019-0309-7
Abstract
Polyketide synthases assemble diverse natural products with numerous important applications. The thioester intermediates in polyketide assembly are covalently tethered to acyl carrier protein domains of the synthase. Several mechanisms for polyketide chain release are known, contributing to natural product structural diversification. Here, we report a dual transacylation mechanism for chain release from the enacyloxin polyketide synthase, which assembles an antibiotic with promising activity against Acinetobacter baumannii. A non-elongating ketosynthase domain transfers the polyketide chain from the final acyl carrier protein domain of the synthase to a separate carrier protein, and a non-ribosomal peptide synthetase condensation domain condenses it with (1S,3R,4S)-3,4-dihydroxycyclohexane carboxylic acid. Molecular dissection of this process reveals that non-elongating ketosynthase domain-mediated transacylation circumvents the inability of the condensation domain to recognize the acyl carrier protein domain. Several 3,4-dihydroxycyclohexane carboxylic acid analogues can be employed for chain release, suggesting a promising strategy for producing enacyloxin analogues.
| Item Type: | Journal Article | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology | |||||||||||||||||||||||||||
| Divisions: | Faculty of Science > Chemistry | |||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Polyketides, Biosynthesis, Organic compounds -- Synthesis, Antibiotics -- Synthesis | |||||||||||||||||||||||||||
| Journal or Publication Title: | Nature Chemistry | |||||||||||||||||||||||||||
| Publisher: | Nature Publishing Group | |||||||||||||||||||||||||||
| ISSN: | 1755-4330 | |||||||||||||||||||||||||||
| Official Date: | October 2019 | |||||||||||||||||||||||||||
| Dates: |
|
|||||||||||||||||||||||||||
| Date of first compliant deposit: | 8 August 2019 | |||||||||||||||||||||||||||
| Volume: | 11 | |||||||||||||||||||||||||||
| Page Range: | 906-912 | |||||||||||||||||||||||||||
| DOI: | 10.1038/s41557-019-0309-7 | |||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
|
|||||||||||||||||||||||||||
| Related URLs: |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
