Light‐Driven Metabolic Pathways in Non‐Photosynthetic Biohybrid Bacteria

Abstract Biomanufacturing via microorganisms relies on carbon substrates for molecular feedstocks and a source of energy to carry out enzymatic reactions. This creates metabolic bottlenecks and lowers the efficiency for substrate conversion. Nanoparticle biohybridization with proteins and whole cell surfaces can bypass the need for redox cofactor regeneration for improved secondary metabolite production in a non‐specific manner. Here we propose using nanobiohybrid organisms (Nanorgs), intracellular protein‐nanoparticle hybrids formed through the spontaneous coupling of core‐shell quantum dots (QDs) with histidine‐tagged enzymes in non‐photosynthetic bacteria, for light‐mediated control of bacterial metabolism. This proved to eliminate metabolic constrictions and replace glucose with light as the source of energy in Escherichia coli , with an increase in growth by 1.7‐fold in 75 % reduced nutrient media. Metabolomic tracking through carbon isotope labeling confirmed flux shunting through targeted pathways, with accumulation of metabolites downstream of respective targets. Finally, application of Nanorgs with the Ehrlich pathway improved isobutanol titers/yield by 3.9‐fold in 75 % less sugar from E. coli strains with no genetic alterations. These results demonstrate the promise of Nanorgs for metabolic engineering and low‐cost biomanufacturing.