Engineering biomimetic ensembles for energy biomanufacturing: from local chemical constraints to functional performance

Abstract

The integration of renewable reducing power with biological C1 assimilation has established energy biomanufacturing as an important direction for low-carbon chemical synthesis under mild, aqueous conditions. Yet pathway-level carbon, electron and cofactor demands are rarely matched at the spatial and temporal scales experienced by individual enzymes. The resulting local constraints remain obscured by bulk measurements. This Review examines these constraints through four overlapping diagnostic lenses: transport, intermediate lifetime, resource allocation, and reaction selectivity. Natural protein shells, membrane-bounded spaces, multienzyme assemblies, and phase-separated domains provide mechanistic precedents for controlling molecular exchange, intermediate retention, cofactor distribution, and reactant concentration. Recent engineering studies have translated these principles into protein microcompartments, encapsulins, scaffolded enzyme assemblies, and biomolecular condensates, while related spatial-control principles have been extended to cell–material reaction environments. Comparison across these systems connects structural assembly with measurable changes in permeability, enzyme stoichiometry, local redox state, pathway flux, and sustained conversion. It also reveals coupled design constraints, because changes that improve retention or local enrichment may alter molecular exchange, cellular resource demand, or responsiveness to fluctuating inputs. Integrating quantitative characterization with kinetic, transport, and metabolic models provides a basis for developing and testing design rules for spatial organization in energy biomanufacturing.

Keywords

biomimetic ensembles / energy biomanufacturing / metabolic compartmentalization / compartmentalized biocatalysis / redox and electron transfer

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Higher Education Press 2027

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