Abstract
Indole-containing acyloins are either key intermediates of many antimicrobial/antiviral natural products or building blocks in the synthesis of biologically active molecules. As such, access to structurally diverse indole-containing acyloins has attracted considerable attention. In this report, we present a pilot study of using biotransformation to provide acyloins that contain various indole substituents. The biotransformation system contains the tryptophan synthase standalone β-subunit variant, PfTrpB6, generated from directed evolution in the literature; a commercially available L-amino acid oxidase (LAAO); and the thiamine-diphosphate (ThDP)-dependent enzyme NzsH, encoded in the biosynthetic gene cluster (nzs) of the bacterial carbazole alkaloid natural product named neocarazostatin A. The utilization of the first two enzymes, the PfTrpB variant and LAAO, is designed to provide structurally diverse indole 3-pyruvate derivatives as donor substrates for NzsH-catalysed biotransformation to provide acyloin derivatives. Our results demonstrate that NzsH displays a considerable substrate profile toward donor substrates for production of acyloins with different indole ring systems, suggesting that NzsH could be further explored as a potential biocatalyst via directed evolution to improve the catalytic efficiency in the future.
Original language | English |
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Article number | 354 |
Number of pages | 10 |
Journal | Molecules |
Volume | 28 |
DOIs | |
Publication status | Published - 1 Jan 2023 |
Bibliographical note
Funding Information:The research was funded by the College of Science and Arts, Jouf University, King Khaled Road, Kingdom of Saudi Arabia, and the Royal Embassy of Saudi Arabia Cultural Bureau in the UK for the PhD scholarship (S.A.); the PhD studentship funded by IBioIC (F.C.), thank the financial supports of Leverhulme Trust-Royal Society Africa award (AA090088) and the jointly funded UK Medical Research Council UK Department for International Development (MRC/DFID) Concordat agreement African Research Leaders Award (MR/S00520X/1) (H.D. and K.K.).
Data Availability Statement
Data are contained within the article.Keywords
- acyloin
- chemoenzymatic synthesis
- indole
- indole-3-pyruvate
- thiamine-diphosphate dependent enzymes
- tryptophan