Breaking down bacterial strategies for complex sugar degradation
Oeiras, 14 November 2023
Gut and soil microbes utilize plant derived-compounds for their metabolism while releasing molecules with human health benefits. Among these, C-glycosides challenge microbial degradation due to a carbon-carbon bond, between glucose and biologically active molecules such as flavones or phenols, which confers remarkable stability to enzymatic and chemical hydrolysis. In a paper recently published in Nature Communications, ITQB NOVA researchers uncovered a critical step employed by soil bacteria to break down these compounds. The research opens new biotechnological avenues for synthesizing novel compounds and pharmaceuticals.
“The analysis of enzyme kinetics, along with product identification, mutagenesis, and structure elucidation, uncovered unique features of a critical catabolic enzyme involved in the degradation of sugar-containing compounds in nature”, says André Taborda, a Ph.D. student at ITQB NOVA and co-first author of the paper. “Investigation of X-ray crystal structures and their dynamic changes allowed understanding substrate recognition, stabilization, and modification during the catalytic mechanism”, adds Ph.D. student Tomás Frazão, the other co-first author, who carried part of the research at Zymvol in the scope of the B-LigZymes project.
With this comprehensive study, researchers clearly distinguished between two similar classes of enzymes, pyranose 2-oxidases, and glycoside 3-oxidases, from the evolutionary, structural, and functional perspectives. These are structurally comparable enzymes but with different functional profiles and ecological significance. “This study enriches our understanding of alternatives that soil bacteria use to obtain sugar in environments where it is not readily available”, states Lígia Martins, head of the Microbial & Enzyme Technology lab. By shedding light on how soil microorganisms handle C-glycosides, this research contributes to fundamental knowledge and opens relevant perspectives for applications in the pharmaceutical, agricultural, and food industries. “We are already working on an engineering approach to optimize this enzyme for biotechnological applications in synthesizing rare sugars and pharmaceutical compounds with antioxidant, anti-inflammatory, and antimicrobial potential in collaboration with our organic chemistry colleague Rita Ventura,” the researcher adds.
This research was carried out by the Microbial and Enzyme Technology, Structural Biology, and Bioorganic Chemistry labs in collaboration with Universitat Autonoma de Barcelona, Universidade do Algarve, and the Barcelona-based company Zymvol that target biocatalyst discovery and optimization through computer-driven innovation.
Original paper: André Taborda & Tomás Frazão et al. Mechanistic Insights into Glycoside 3-Oxidases Involved in C-Glycoside Metabolism in Soil Microorganisms. Nature Communications (2023).
