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Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase

Journal Article · · Journal of the American Chemical Society
DOI:https://doi.org/10.1021/jacs.3c02446· OSTI ID:1985981
 [1];  [2];  [3];  [4];  [4];  [5];  [6];  [4]
  1. Princeton University, NJ (United States); Shanghai Jiao Tong University (China); Princeton University
  2. Princeton University, NJ (United States); Cornell University, Ithaca, NY (United States)
  3. CNR-Institute of Nanoscience, Modena (Italy)
  4. Princeton University, NJ (United States)
  5. University of L’Aquila (Italy)
  6. Cornell University, Ithaca, NY (United States)
+ Show Author Affiliations
Photoenzymes are a rare class of biocatalysts that use light to facilitate chemical reactions. Many of these catalysts utilize a flavin cofactor to absorb light, suggesting that other flavoproteins might have latent photochemical functions. Lactate monooxygenase is a flavin-dependent oxidoreductase previously reported to mediate the photodecarboxylation of carboxylates to afford alkylated flavin adducts. While this reaction holds a potential synthetic value, the mechanism and synthetic utility of this process are unknown. Here, we combine femtosecond spectroscopy, site-directed mutagenesis, and a hybrid quantum-classical computational approach to reveal the active site photochemistry and the role the active site amino acid residues play in facilitating this decarboxylation. Light-induced electron transfer from histidine to flavin was revealed, which has not been reported in other proteins. These mechanistic insights enable the development of catalytic oxidative photodecarboxylation of mandelic acid to produce benzaldehyde, a previously unknown reaction for photoenzymes. Furthermore, our findings suggest that a much wider range of enzymes have the potential for photoenzymatic catalysis than has been realized to date.
Research Organization:
Cornell University, Ithaca, NY (United States); Princeton University, NJ (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0019370
OSTI ID:
1985981
Journal Information:
Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 24 Vol. 145; ISSN 0002-7863
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English

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Figures / Tables (6)

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Figure 6(p. 23)figure Figure 6

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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