Back to Search Start Over

Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains

Authors :
Qingpei Liu
Dan Zhang
Shuaibiao Gao
Xianhua Cai
Ming Yao
Yao Xu
Yifu Gong
Ke Zheng
Yigui Mao
Liyan Yang
Dengfeng Yang
István Molnár
Xiaolong Yang
Source :
Liu, Q, Zhang, D, Gao, S, Cai, X, Yao, M, Xu, Y, Gong, Y, Zheng, K, Mao, Y, Yang, L, Yang, D, Molnár, I & Yang, X 2023, ' Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains ', Angewandte Chemie-International Edition, vol. 62, no. 6, e202214379 . https://doi.org/10.1002/anie.202214379
Publication Year :
2022

Abstract

Orsellinic acid (OA) derivatives are produced by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Here, we use combinatorial domain exchanges, domain dissections and reconstitutions to reveal that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. We show that artificial SAT-TE fusion proteins are highly effective catalysts and reprogram the ketide homologation chassis to form didepsides. We also demonstrate that dissected SAT and TE domains of Preu6 physically interact, and SAT and TE domains of OA-synthesizing nrPKSs may co-evolve. Our work highlights an unexpected domain–domain interaction in nrPKSs that must be considered for the combinatorial biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.

Details

ISSN :
15213773
Database :
OpenAIRE
Journal :
Angewandte Chemie (International ed. in English)
Accession number :
edsair.doi.dedup.....87a232eb71d5465d439d5e1c05fe7683
Full Text :
https://doi.org/10.1002/anie.202214379