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.