Designing biocatalytic cascades with precise control over coenzyme regeneration, efficiency, and selectivity remains a central challenge in biocatalysis. Here, we present a sustainable strategy for constructing covalently bonded multienzyme complexes (CBMEs) that enable efficient redox biosynthesis under mild and environmentally friendly conditions. A quantitative reaction–diffusion model was developed to elucidate spatial organization within CBMEs, introducing a G factor that quantitatively predicts the adaptation efficiency (ε) of dual-enzyme systems by integrating geometric and kinetic parameters. Guided by this model, a dual-enzyme complex for l-amino acid biosynthesis achieved over 99% conversion within 2 h and >99.9% enantiomeric excess, while significantly reducing coenzyme use and reaction waste. This work demonstrates that controlling enzyme spatial arrangement through covalent coupling not only enhances catalytic efficiency and selectivity but also provides a green and sustainable framework for designing high-performance bioredox systems.
Du et al. (Sat,) studied this question.