Theoretical study on role of aliphatic aldehyde in bacterial bioluminescence

Abstract

Bacterial bioluminescence (BL) has been widely applied in environmental toxin monitoring, drug screening, and in vivo imaging. In bacterial BL, an aliphatic aldehyde (RCHO) is indispensable. The RCHO involved in wild bacterial BL is of 14 carbon atoms, and only those RCHO molecules with carbon chain lengths from 8 to 16 carbon atoms generate BL. Why the RCHO chain must have carbon atoms from 8 to16? How does such RCHO take part in the related reaction to produce BL? Both questions still remain largely unknown. In this article, in real protein environment, we explored the selectivity of RCHO chain length and the chemical reaction involving RCHO in bacterial BL via molecular docking, combined quantum mechanics and molecular mechanics (QM/MM) calculation, and molecular dynamics (MD) simulation. The theoretical investigation indicates: RCHO is wrapped by nine amino acid residues, which form a hydrophobic cavity in bacterial luciferase. The cavity size affects the effective binding of RCHO of different chain length with the nearby residues. The RCHO molecules with chain length of 8 to 16 carbon atoms participate in an enzymatic addition reaction to produce a high-energy intermediate, which is the energy source for light emission. The enzymatic addition reaction is via a concert proton relay process, which disagree with the experimental proposal that αHis44 abstracts a proton to initiate the addition reaction. It is a water molecule that abstracts and relays a proton to catalyze the reaction, while αHis44 stabilizes the water molecule and the six-center transition state of the reaction in bacterial luciferase. This study clearly interprets the role of the long chain RCHO in bacterial BL.