Transporter annotations are holding up progress in metabolic modeling

Autor: John Casey, Brian Bennion, Patrik D’haeseleer, Jeffrey Kimbrel, Gianna Marschmann, Ali Navid
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Systems Biology, Vol 4 (2024)
Druh dokumentu: article
ISSN: 2674-0702
DOI: 10.3389/fsysb.2024.1394084
Popis: Mechanistic, constraint-based models of microbial isolates or communities are a staple in the metabolic analysis toolbox, but predictions about microbe-microbe and microbe-environment interactions are only as good as the accuracy of transporter annotations. A number of hurdles stand in the way of comprehensive functional assignments for membrane transporters. These include general or non-specific substrate assignments, ambiguity in the localization, directionality and reversibility of a transporter, and the many-to-many mapping of substrates, transporters and genes. In this perspective, we summarize progress in both experimental and computational approaches used to determine the function of transporters and consider paths forward that integrate both. Investment in accurate, high-throughput functional characterization is needed to train the next-generation of predictive tools toward genome-scale metabolic network reconstructions that better predict phenotypes and interactions. More reliable predictions in this domain will benefit fields ranging from personalized medicine to metabolic engineering to microbial ecology.
Databáze: Directory of Open Access Journals