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

MARIA LAURA MASCOTTI; MAXIMILIANO JURI AYUB; NICHOLAS FURNHAM; JANET M THORNTON; ROMAN A LASKOWSKI

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016

0022-2836

Flavin-dependent monooxygenases play a variety of keyphysiological roles and are also very powerful biotechnological tools.These enzymes have been classified into eight different classes (A-H)based on their sequences and biochemical features. By combiningstructural and sequence analysis, as well as phylogenetic inference, wehave explored the evolutionary history of classes A, B, E, F and G, anddemonstrate that their multi-domain architectures reflect theirphylogenetic relationships, suggesting that the main evolutionary stepsin their divergence are likely to have arisen from the recruitment ofdifferent domains. Additionally, the functional divergence within in eachclass appears to have been the result of other mechanisms such as acomplex set of single-point mutations. Our results reinforce the ideathat a main constraint on the evolution of cofactor-dependent enzymes isthe functional binding of the cofactor. Additionally, a remarkablefeature of this family is that the sequence of the key FAD-binding domainis split into at least two parts in all classes studied here, a featurerarely observed in other protein families. We propose a complex set ofevolutionary events that gave rise to the origin of the different classeswithin this family.