Chopping and changing: the evolution of the flavin-dependent monooxygenases

MASCOTTI, ML; JURI AYUB, M; FURNHAM, N; THORNTON, JM; LASKOWSKI, RA

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016

0022-2836

Flavin-dependent monooxygenases play a variety of key physiological roles and are also very powerful biotechnological tools. These enzymes have been classified into eight different classes (A?H) based on theirsequences and biochemical features. By combining structural and sequence analysis, and phylogenetic inference, we have explored the evolutionary history of classes A, B, E, F, and G and demonstrate that theirmultidomain architectures reflect their phylogenetic relationships, suggesting that the main evolutionary steps in their divergence are likely to have arisen from the recruitment of different domains. Additionally, thefunctional divergence within in each class appears to have been the result of other mechanisms such as a complex set of single-point mutations. Our results reinforce the idea that a main constraint on the evolution ofcofactor-dependent enzymes is the functional binding of the cofactor. Additionally, a remarkable feature of this family is that the sequence of the key flavin adenine dinucleotide-binding domain is split into at least two partsin all classes studied here. We propose a complex set of evolutionary events that gave rise to the origin of the different classes within this family.