Photochemical mechanism of light-driven fatty acid photodecarboxylase

Derren J. Heyes, Balaji Lakavath, Samantha J. O. Hardman, Michiyo Sakuma, Tobias M. Hedison, Nigel S. Scrutton

Research output: Contribution to journalArticlepeer-review


Fatty acid photodecarboxylase (FAP) is a promising target for the production of biofuels and fine chemicals. It contains a flavin adenine dinucleotide cofactor and catalyzes the blue-light dependent decarboxylation of fatty acids to generate the corresponding alkane. However, little is known about the catalytic mechanism of FAP, or how light is used to drive enzymatic decarboxylation. Here, we have used a combination of time-resolved and cryogenic trapping UV-visible absorption spectroscopy to characterize a red-shifted flavin intermediate observed in the catalytic cycle of FAP. We show that this intermediate can form below the ‘glass transition’ temperature of proteins, whereas the subsequent decay of the species proceeds only at higher temperatures, implying a role for protein motions in the decay of the intermediate. Solvent isotope effect measurements, combined with analyses of selected site-directed variants of FAP, suggest that formation of the red-shifted flavin species is directly coupled with hydrogen atom transfer from a nearby active site cysteine residue yielding the final alkane product. Our study suggests that this cysteine residue forms a thiolate-flavin charge transfer species, which is assigned as the red-shifted flavin intermediate. Taken together, our data provide new insights into light-dependent decarboxylase mechanisms catalyzed by FAP and highlight important considerations in the (re)design of novel flavin-based photoenzymes.
Original languageEnglish
Pages (from-to)6691-6696
Number of pages6
JournalACS Catalysis
Issue number12
Early online date19 May 2020
Publication statusPublished - 19 Jun 2020


  • charge transfer
  • decarboxylation
  • fatty acid photodecarboxylase
  • flavin
  • photoenzyme
  • red-shifted species
  • thiolate

Research Beacons, Institutes and Platforms

  • Manchester Institute of Biotechnology


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