Chemoenzymatic Synthesis of Indole-Containing Acyloin Derivatives

Saad Alrashdi, Federica Casolari, Aziz Alabed, Kwaku Kyeremeh, Hai Deng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
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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 languageEnglish
Article number354
Number of pages10
Publication statusPublished - 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.


  • acyloin
  • chemoenzymatic synthesis
  • indole
  • indole-3-pyruvate
  • thiamine-diphosphate dependent enzymes
  • tryptophan


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