Chopping and Changing: the Evolution of the Flavin-dependent Monooxygenases

• Published in: Journal of molecular biology 2016-07, Vol.428 (15), p.3131-3146
• Main Authors: Mascotti, Maria Laura, Juri Ayub, Maximiliano, Furnham, Nicholas, Thornton, Janet M., Laskowski, Roman A.
• Format: Article
• Language: English
• Subjects: Biological Evolution; Coenzymes - metabolism; cofactor-binding enzymes; enzyme evolution; flavin-dependent monooxygenases; Flavins - metabolism; Mixed Function Oxygenases - metabolism; multidomain architecture; Phylogeny; Protein Domains - physiology; Sequence Analysis - methods
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2016.07.003

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 their sequences 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 their multidomain 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, the functional 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 of cofactor-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 parts in 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. [Display omitted] •Changes in domain architectures reflect the phylogeny of flavin monooxygenases.•Recruitment of different domains has been the main force driving its evolution.•A notable feature of flavin monooxygenases is that the flavin adenine dinucleotide-binding domain is split.•Classes of monooxygenases emerged from an ancestral domain by structural changes.