Decoding the landscape in biomanufacturing of xylose: metabolic bottlenecks and computation-assisted strategies.

Xylose utilization in lignocellulosic biomanufacturing is limited by carbon catabolite repression and missing natural pathways, wasting nearly 40% of available carbohydrate sources.

• Why it matters: This bottleneck reduces biorefinery economic competitiveness and slows progress toward large-scale, sustainable production from lignocellulose-derived sugars.
• What they did: The review synthesizes xylose metabolism pathways, emphasizing rate-limiting enzymes, cofactor preferences, feedback regulation, and compartmentalization, and discusses modifying these enzymes to improve carbon flux. It also outlines AI-driven protein engineering combined with genome-scale metabolic models to address enzyme limitations and redox imbalances.
• The result: Integrating AI protein engineering with genome-scale metabolic modeling is presented as a framework that optimizes key enzymes and corrects cofactor dependencies, enabling more efficient xylose conversion.

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