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This multiscale three-zone reactive mixing model provides a theoretical framework for engineering a scale separation in batch enzymatic hydrolysis of cellulose to strategize significant leaps in glucose yields. Formulated using the Liapunov–Schmidt method of the classical bifurcation theory, our model explores the multiscale spatiotemporal dynamics between the fundamental processes of macromixing (convection) and micromixing (diffusion) of the enzymes (Endoglucanase, Exoglucanase, β -glucasidase) and reducing sugars, adsorption and desorption of enzymes on the solid cellulosic substrates, and the product-inhibited liquid and solid phase enzymatic reactions that depolymerize microcrystalline cellulose (Avicel). The model is validated for a range of substrate loadings (2–5%) using our experimental results for the two asymptotic cases of no mixing and continuous mixing, as well as for the macro/micro scale-separated optimal mixing strategy that increases the glucose yield by up to 26% by macromixing completely for an initial period followed by micromixing for the remaining duration of the hydrolysis. [ABSTRACT FROM AUTHOR]