Design an Energy‐Conserving Pathway for Efficient Biosynthesis of 1,5‐Pentanediol and 5‐Amino‐1‐Pentanol

ABSTRACT 1,5‐Pentanediol (1,5‐PDO) is an important five‐carbon alcohol, widely used in polymer and pharmaceutical industries. Considering the substantial energy (ATP and NADPH) requirements of previous pathways, an energy‐conserving artificial pathway with a higher theoretical yield (0.75 mol/mol glucose) was designed and constructed in this study. In this pathway, lysine is converted into 1,5‐PDO by decarboxylation, two transamination, and two reduction reactions. For the purpose of full pathway construction, 5‐aminopetanal reductase and 5‐amino‐1‐pentanol (5‐APO) transaminase were identified and characterized. By implementing strategies such as modular optimization of gene expression, enhancing lysine biosynthesis and increasing NADPH supply, the engineered strains were able to produce 1502.8 mg/L 5‐APO and 726.2 mg/L 1,5‐PDO in shake flasks and 11.7 g/L 1,5‐PDO in a 3 L bioreactor. This work provides a new and promising pathway for the efficient production of 5‐APO and 1,5‐PDO.