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Studying a bottleneck of multimodular polyketide synthase processing : the polyketide structure-dependent performance of ketoreductase domains

Title data

Schröder, Marius ; Roß, Theresa ; Hemmerling, Franziska ; Hahn, Frank:
Studying a bottleneck of multimodular polyketide synthase processing : the polyketide structure-dependent performance of ketoreductase domains.
In: ACS Chemical Biology. Vol. 17 (2022) Issue 5 . - pp. 1030-1037.
ISSN 1554-8937
DOI: https://doi.org/10.1021/acschembio.2c00047

Project information

Project financing: This work was supported by an Exploration Grant of the Boehringer Ingelheim Foundation (BIS), a Material Cost Allowance of the Fund of the Chemical Industry (FCI).

Abstract in another language

Ketoreductases (KRs) are canonical domains of type I polyketide synthases (PKSs). They stereoselectively reduce ACP-bound β-ketothioester intermediates and are responsible for a large part of the stereocenters in reduced polyketides. Albeit essential for the understanding and engineering of PKS, the specific effects of altering the polyketide part of KR precursors on their performance has rarely been studied. We present investigations on the substrate-dependent performance of six isolated KR domains using a library of structurally diverse surrogates for PKS thioester intermediates. A pronounced correlation between the polyketide structure and the KR performance was observed with activity and stereoselectivity diminishing with growing deviation from the natural KR precursor structure. The extent of this decrease and the profile of arising side products was characteristic for the individual KRs. Our results reinforce the importance of structure−KR performance relationships and suggest extended studies with isolated domains and whole PKS modules.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professor Organic Chemistry - Food Chemistry > Professor Organic Chemistry - Food Chemistry - Univ.-Prof. Dr. Frank Hahn
Profile Fields > Emerging Fields > Food and Health Sciences
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professor Organic Chemistry - Food Chemistry
Profile Fields
Profile Fields > Emerging Fields
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 25 Apr 2022 09:27
Last Modified: 08 Jun 2022 06:20
URI: https://eref.uni-bayreuth.de/id/eprint/69154