A Natural Diels-Alder Biocatalyst Enables Efficient [4 + 2] Cycloaddition Under Harsh Reaction Conditions

Carl O Marsh, Nicholas R Lees, Li-Chen Han, Matthew J Byrne, Sbu Z Mbatha, Laurence Maschio, Sebastian Pagden-Ratcliffe, Philip Duke, James E M Stach, Paul Curnow, Chris L Willis, Paul R Race

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
42 Downloads (Pure)

Abstract

Carbon‐carbon bond formation is a fundamental transformation in both synthetic chemistry and biosynthesis. Enzymes catalyze such reactions with exquisite selectivity which often cannot be achieved using non‐biological methods but may suffer from an intolerance of high temperature and the presence of organic solvents limiting their applications. Here we report the thermodynamic and kinetic stability of the β‐barrel natural Diels‐Alderase AbyU, which catalyzes formation of the spirotetronate core of the antimicrobial natural product abyssomicin C, with creation of 3 new asymmetric centers. This enzyme is shown to catalyze [4 + 2] cycloadditions at elevated temperature (up to 65 oC), and in the presence of organic solvents (MeOH, CH3CN and DMSO) and the chemical denaturant guanidinium hydrochloride, revealing that AbyU has potential widespread value as a biocatalyst.
Original languageEnglish
Number of pages6
JournalChemCatChem
Early online date25 Aug 2019
DOIs
Publication statusE-pub ahead of print - 25 Aug 2019

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute
  • BCS and TECS CDTs

Keywords

  • cycloaddition
  • protein folding
  • natural products
  • Diels-Alderase
  • Biocatalysis
  • Synthetic biology

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