Elucidating the Metabolic Landscape of p‑Coumaric Acid to Deepen Biological Implication and Enhance Biomanufacturing

p-Coumaric acid (p-CA) is a universal
precursor of plant lignin and polyphenols. A comprehensive understanding
of p-CA metabolism is essential for elucidating biological
evolution, advancing polyphenol biomanufacturing, and developing lignocellulosic
biorefineries. However, p-CA metabolism remains poorly
characterized due to the limited number of studies and the absence
of universal prediction methods. Here, we systematically elucidate p-CA metabolism in the industrial yeast Yarrowia
lipolytica. Through transcriptomic analysis and a reaction-based
prediction method, we identify key degradation genes in Y.
lipolytica, whose collective deletion reduced p-CA degradation by 81.6% and increased production by 2.51-fold. Comparative
analysis of 109 species revealed that the metabolic potential for p-CA is widespread but exhibits significant habitat-dependent
divergence. This study establishes a systematic framework for understanding
and engineering p-CA metabolism, providing insights
for optimizing microbial cell factories and a broader exploration
of metabolic pathways.