From cell factories to photobiocatalysts: reengineering cyanobacteria for solar-driven chemical manufacturing

To achieve more sustainable, light-powered chemical manufacturing, cyanobacterial engineering is expanding from conventional carbon-accumulating “cell factories” toward the complementary use of cyanobacteria as “whole-cell photobiocatalysts.” This review critically examines this conceptual extension. By shifting the engineering focus from carbon-centric biosynthesis to electron- and energy-coupled catalysis, this emerging approach partially decouples target-product formation from the de novo assembly of CO2-derived carbon skeletons. Instead, it exploits photosynthetically generated reducing equivalents and ATP to support redox and energy-dependent enzymatic transformations, thereby reducing dependence on external cofactor- or energy-regeneration systems. We outline a multidimensional engineering framework that integrates carbon-flux redirection (“push”), coupling to photosynthetically generated reducing equivalents and ATP (“drive”), and product-removal-driven “pull” through secretion, volatilization, or in situ extraction. We further highlight advances in light-tolerant and stress-robust cyanobacterial chassis, together with emerging process strategies based on attached-growth and biofilm photobioreactors. We also critically consider genetic instability, variable enzyme-coupling efficiency, and scale-dependent light and mass-transfer limitations. Finally, we discuss the biophysical and energetic limits of light-to-chemical conversion, competition for reducing power, the largely conceptual potential of temporally decoupled light harvesting and dark-phase catalysis, and the need to select economically viable target products using rigorous techno-economic and life-cycle analyses. Collectively, this review provides conceptual and practical guidance for developing sustainable photosynthetic biomanufacturing platforms.