Combining enzyme and metabolic engineering for microbial supply of therapeutic phytochemicals

The history of pharmacology is deeply intertwined with plant-derived compounds, which continue to be crucial in drug development. However, their complex structures and limited availability in plants challenge drug discovery, optimization, development, and industrial production via chemical synthesis or natural extraction. This review delves into the integration of metabolic and enzyme engineering to leverage micro-organisms as platforms for the sustainable and reliable production of therapeutic phytochemicals. We argue that engineered microbes can serve a triple role in this paradigm: facilitating pathway discovery, acting as cell factories for scalable manufacturing, and functioning as platforms for chemical derivatization. Analyzing recent progress and outlining future directions, the review highlights microbial biotechnology's transformative potential in expanding plant-derived human therapeutics’ discovery and supply chains.