Synthetic Biology Strategies for Engineering Microbial Cell Factories toward Efficient p -Coumaric Acid Biosynthesis

Abstract p-Coumaric acid (p-CA) is a high-value phenolic acid with applications in food preservation, pharmaceuticals, cosmetics, and the production of plant-derived aromatic compounds. Microbial cell factories provide a sustainable alternative to plant extraction and chemical synthesis. In this review, recent advances in synthetic biology strategies for microbial p-CA biosynthesis are systematically summarized. The natural biosynthetic pathways and major heterologous routes are first introduced, followed by a review of key enzyme engineering strategies. Furthermore, metabolic engineering approaches for increasing precursor availability, enhancing metabolic flux, attenuating competing branches, blocking degradation pathways, and optimizing cofactor and transporter systems are discussed. Emerging model-guided and machine learning-assisted strategies for rational strain optimization are also highlighted. Finally, progress in chassis reinforcement, substrate expansion, and fermentation process optimization is summarized, and future opportunities for constructing robust, efficient, and industrially applicable p-CA-producing microbial cell factories are discussed.