Genome Mining of Oxidation Modules in trans-Acyltransferase Polyketide Synthases Reveals a Culturable Source for Lobatamides

R. Ueoka, R.A. Meoded, A. Gran-Scheuch, A. Bhushan, M.W. Fraaije, J. Piel

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimBacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are multimodular megaenzymes that biosynthesize many bioactive natural products. They contain a remarkable range of domains and module types that introduce different substituents into growing polyketide chains. As one such modification, we recently reported Baeyer–Villiger-type oxygen insertion into nascent polyketide backbones, thereby generating malonyl thioester intermediates. In this work, genome mining focusing on architecturally diverse oxidation modules in trans-AT PKSs led us to the culturable plant symbiont Gynuella sunshinyii, which harbors two distinct modules in one orphan PKS. The PKS product was revealed to be lobatamide A, a potent cytotoxin previously only known from a marine tunicate. Biochemical studies show that one module generates glycolyl thioester intermediates, while the other is proposed to be involved in oxime formation. The data suggest varied roles of oxygenation modules in the biosynthesis of polyketide scaffolds and support the importance of trans-AT PKSs in the specialized metabolism of symbiotic bacteria.
Original languageEnglish
Pages (from-to)7761-7765
JournalAngewandte Chemie - International Edition
Volume59
Issue number20
DOIs
Publication statusPublished - 11 May 2020
Externally publishedYes

Funding

We thank Young Ryun Chung and Dmitri Mavrodi for discussions on the biology of G. sunshinyii. This project was funded by the SNSF (grant IDs 205321_165659 and 205320_185077), and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 742739). We thank Young Ryun Chung and Dmitri Mavrodi for discussions on the biology of . This project was funded by the SNSF (grant IDs 205321_165659 and 205320_185077), and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 742739). G. sunshinyii

FundersFunder number
Young Ryun Chung and Dmitri Mavrodi
Horizon 2020 Framework Programme
European Research Council
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung205320_185077, 205321_165659
Horizon 2020742739

    Fingerprint

    Dive into the research topics of 'Genome Mining of Oxidation Modules in trans-Acyltransferase Polyketide Synthases Reveals a Culturable Source for Lobatamides'. Together they form a unique fingerprint.

    Cite this