Evolution of substrate specificity in a recipient's enzyme following horizontal gene transfer

Lianet Noda-García, Aldo R. Camacho-Zarco, Sofía Medina-Ruíz, Paul Gaytán, Mauricio Carrillo-Tripp, Vilmos Fülöp, Francisco Barona-Gómez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Despite the prominent role of horizontal gene transfer (HGT) in shaping bacterial metabolism, little is known about the impact of HGT on the evolution of enzyme function. Specifically, what is the influence of a recently acquired gene on the function of an existing gene? For example, certain members of the genus Corynebacterium have horizontally acquired a whole l-tryptophan biosynthetic operon, whereas in certain closely related actinobacteria, for example, Mycobacterium, the trpF gene is missing. In Mycobacterium, the function of the trpF gene is performed by a dual-substrate (βα)8 phosphoribosyl isomerase (priA gene) also involved in l-histidine (hisA gene) biosynthesis. We investigated the effect of a HGT-acquired TrpF enzyme upon PriA's substrate specificity in Corynebacterium through comparative genomics and phylogenetic reconstructions. After comprehensive in vivo and enzyme kinetic analyses of selected PriA homologs, a novel (βα)8 isomerase subfamily with a specialized function in l-histidine biosynthesis, termed subHisA, was confirmed. X-ray crystallography was used to reveal active-site mutations in subHisA important for narrowing of substrate specificity, which when mutated to the naturally occurring amino acid in PriA led to gain of function. Moreover, in silico molecular dynamic analyses demonstrated that the narrowing of substrate specificity of subHisA is concomitant with loss of ancestral protein conformational states. Our results show the importance of HGT in shaping enzyme evolution and metabolism.

Original languageAmerican English
Pages (from-to)2024-2034
Number of pages11
JournalMolecular Biology and Evolution
Issue number9
StatePublished - Sep 2013
Externally publishedYes


  • amino acid metabolism
  • enzyme evolution
  • horizontal gene transfer


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