Project information
Unlocking the unused capacity of bacterial metabolism through the rational design of substrate transporters (UNLOCK)

Bacteria are essential biocatalysts, but their efficiency in biochemical production is limited by low carbon flux and productivity. Evidence suggests that bacterial metabolism has untapped capacity, with many catabolic enzymes operating below their maximum rates. This project aims to unlock this dormant potential using a novel “carbon PUSH” strategy, wherein engineered high-performance transporters saturate catabolic enzymes with sugar substrates. The study will investigate the reproducibility of this strategy across three substrates and three bacterial species while advancing the design and validation of efficient substrate transporters. Key objectives include molecular dynamics simulations of sugar transport via the Glf facilitator from Zymomonas mobilis and AI-driven computational design and testing of Glf variants with altered specificity and stability in selected bacterial hosts. By combining different substrates and bacteria, this research seeks to elucidate metabolic bottlenecks and develop enhanced bacterial transporters, paving the way for more efficient biotechnologies.