Combinatorial Enzymatic Synthesis of Unnatural Long-Chain β-Branch Pyrones by a Highly Promiscuous Enzyme

Lixia Pan; Lilan Yang; Yanbing Huang; Yongyuan Liang; Qihuan He; Dengfeng Yang

doi:10.1021/acsomega.9b02473

Combinatorial Enzymatic Synthesis of Unnatural Long-Chain β-Branch Pyrones by a Highly Promiscuous Enzyme

ACS Omega. 2019 Dec 5;4(25):21078-21082. doi: 10.1021/acsomega.9b02473. eCollection 2019 Dec 17.

Authors

Lixia Pan¹, Lilan Yang¹, Yanbing Huang¹, Yongyuan Liang¹, Qihuan He¹, Dengfeng Yang¹

Affiliation

¹ Guangxi Key Laboratory of Biorefinery, Guangxi Biomass Industrialization Engineering Institute, National Engineering Research Center of Non-food Biorefinery, State Key Laboratory of Non-Food Biomass and Enzyme Technology and Guangxi Key Laboratory of Marine Natural Products and Combinatorial Biosynthesis Chemistry, Guangxi Beibu Gulf Marine Research Center, Guangxi Academy of Sciences, Nanning 530007, Guangxi, China.

Abstract

In this study, we described in detail a combinatorial enzymatic synthesis approach to produce a series of unnatural long-chain β-branch pyrones. We attempted to investigate the catalytic potential of a highly promiscuous enzyme type III PKS to catalyze the non-decarboxylative condensation reaction by two molecules of fatty acyl diketide-N-acetylcysteines (diketide-NACs) units. Two non-natural long-chain (C₁₆, C₁₈) fatty acyl diketide-NACs were prepared successfully for testing the ability of non-decarboxylative condensation. In vitro, 12 novel naturally unavailable long-chain β-branch pyrones were generated by one-pot formation and characterized by ultraviolet-visible spectroscopy and high-resolution liquid chromatography-mass spectrometry. Interestingly, enzymatic kinetics result displays that this enzyme exhibits the remarkable compatibility to various non-natural long-chain substrates. These results would be useful to deeply understand the catalytic mechanism of this enzyme and further extend the application of enzymatic synthesis of non-natural products.