Mechanisms of reduced flavin transfer in the two-component flavin-dependent monooxygenases

Two-component flavin-dependent enzymes are abundant in nature and are involved in a wide variety of biological reactions. These enzymes consist of a reductase which generates a reduced flavin and a monooxygenase that utilizes the reduced flavin as a substrate for monooxygenation. As reduced flavin is unstable and can be oxidized by oxygen, these enzymes must have a means to efficiently coordinate the transfer of the reduced flavin such that auto-oxidation can be minimized. Various types of experiments and methodologies have been used to probe the mode of reduced flavin transfer. Results from many systems have indicated that the transfer can be achieved by free diffusion and that the presence of one component has no influence on the kinetics of the other component. Contradicting results indicating that the transfer of the reduced flavin may be achieved via protein-protein mediation also exist. Regardless of the mode of reduced flavin transfer, these enzymes have a means to control their overall kinetics such that the reaction rate is slow when the demand for oxygenation is not high. (C) 2014 Elsevier Inc. All rights reserved.