Crystal Structure of a 4,6-α-Glucanotransferase Supports Diet-Driven Evolution of GH70 Enzymes from α-Amylases in Oral Bacteria

The human diet has been subject to dramatic changes due to food processing and refining. However, whether this affected the evolution of enzymes in human microbiota is largely unknown. It was proposed that glycoside hydrolase family 70 (GH70) glucansucrases (GS) from Lactobacilli, which synthesize α-glucan-type extracellular polysaccharides (EPS) from sucrose, evolved from GH13 starch-acting α-amylases, via GH70 4,6-α-glucanotransferases (4,6-α-GT).
We determined the first crystal structure of a 4,6-α-glucanotransferase (GTFB from L. reuteri 121); its unique active site details the structural changes accompanying such an evolutionary pathway. Both GS and 4,6-α-GT enzymes synthesize EPS in vivo, but from either sucrose or starch(-derivatives), respectively. Genomic and phylogenetic data further support the idea that dietary changes involving starch (derivatives) and sucrose intake were critical factors during the evolution of 4,6-α-GTs and (later) GSs from α-amylases, allowing oral bacteria to produce extracellular polymers that contribute to biofilm formation.