Abstract 1891 Exploring Tyrosine Metabolism: Examining the implications of competition within a microbial community and the health consequences arising from the rivalry between a gut microbial pathway and the human pathway

Tyrosine, a versatile amino acid crucial for protein synthesis, undergoes diverse conversions leading to both beneficial and detrimental metabolites. The modulation of these metabolite levels results from direct competition among different metabolic pathways responsible for tyrosine breakdown, whether it be the competition between distinct microbes or the rivalry between a microbe and its host. This study aims to understand the breakdown of tyrosine through two distinct scenarios: 1) within a microbial community, and 2) during a competition between a microbe and a host. Our objectives include understanding the mechanisms of these competitions, discerning the metabolic outcomes, and identifying the efficiency of different pathways. To achieve this, we constructed a synthetic microbial community comprising various E. coli strains, each differing solely by the presence of a specific enzyme from a distinct tyrosine metabolic pathway. To assess metabolic outcomes in these communities, we developed a tool employing a phenotypic assay. Our findings reveal that breakdown product levels vary based on the type and combination of metabolic pathways within the community, with the metabolic outcome directly proportional to strain ratios. The methodologies employed in this study include SDS-PAGE analysis, genetic manipulation, colorimetric assays, phenotypic assays, and HPLC. Moreover, the inability to metabolize tyrosine resulting from a flawed tyrosine breakdown pathway in humans contributed to diverse metabolic disorders such as tyrosinemias (I, II, III), hawkinsinuria, and alkaptonuria. Utilizing the tool derived from our experiments on tyrosine breakdown within a microbial community, we illustrate a potential metabolic diversion of the human tyrosine breakdown pathway facilitated by a gut microbial enzyme. This approach holds promise as a novel therapeutic intervention for addressing metabolic disorders associated with the human tyrosine breakdown pathway. We thank the New College of Interdisciplinary Arts and Sciences (NCIAS) at Arizona State University for the funding support.