Revisiting the Origin of Bacterial Bioluminescence: QM/MM Study on Oxygenation Reaction of Reduced Flavin in Protein

• Published in: Chemphyschem 2019-02, Vol.20 (3), p.405-409
• Main Authors: Luo, Yanling, Liu, Ya‐Jun
• Format: Article
• Language: English
• Subjects: Bacteria; bacterial bioluminescence; Biological activity; Bioluminescence; Biosynthesis; Catalysis; Electron transfer; Homeostasis; Metabolism; Molecular dynamics; Oxygenation; PCET; photochemistry; Proteins; Quantum mechanics; reaction mechanism
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201800970

Bacterial bioluminescence is initiated by the oxygenation reaction of reduced flavin mononucleotide in luciferase. This enzymatic oxygenation occurs in a wide range of biological processes including cellular redox metabolism, biocatalysis, biosynthesis and homeostasis. However, little is known about the mechanism of the enzymatic reaction between singlet reduced flavin and triplet oxygen. To explore the enigmatic oxygenation, for the first time, the reaction of reduced flavin anion with oxygen was studied in bacterial luciferase by a combined quantum mechanics and molecular mechanics method as well as molecular dynamics simulation. The calculated results demonstrate that the reaction proceeds via a proton‐coupled electron transfer (PCET) pathway, and the essential αHis44 acts as a catalytic acid to provide the proton. The currently proposed PCET mechanism clearly describes the initial steps of bacterial bioluminescence, and could be suitable for the other flavin oxygenation reactions in enzymes. Bacterial bioluminescence: For the first time, the oxygenation reaction of reduced flavin was theoretically studied in bacterial luciferase. The calculated results demonstrate a PCET mechanism of formation‐annihilation of FMNH⋅/HOO⋅/HIE44 radical pair.