Understanding Bacterial Bioluminescence: A Theoretical Study of the Entire Process,from Reduced Flavin to Light Emission

Bacterial bioluminescence (BL) has been successfully applied in water‐quality monitoring and in vivo imaging. The attention of researchers has been attracted for several decades, but the mechanism of bacterial BL is still largely unknown due to the complexity of the multistep reaction process. Debates mainly focus on three key questions: How is the bioluminophore produced? What is the exact chemical form of the bioluminophore? How does the protein environment affect the light emission? Using quantum mechanics (QM), combined QM and molecular mechanics (QM/MM) and molecular dynamic (MD) calculations in gas‐phase, solvent and protein environments, the entire process of bacterial BL was investigated, from flavin reduction to light emission. This investigation revealed that: 1) the chemiluminescent decomposition of flavin peroxyhemiacetal does not occur through the intramolecular chemical initiated electron exchange luminescence (CIEEL) or the “dioxirane” mechanism, as suggested in the literature. Instead, the decomposition occurs according to the charge‐transfer initiated luminescence (CTIL) mechanism for the thermolysis of dioxetanone. 2) The first excited state of 4a‐hydroxy‐4a,5‐dihydroFMN (HFOH) was affirmed to be the bioluminophore of bacterial BL. This study provides details regarding the mechanism by which bacterial BL is produced and is helpful in understanding bacterial BL in general.