Systems and synthetic biology for plant natural product pathway elucidation

Plants are one of the major reservoirs of medicinal compounds, serving as a cornerstone of both traditional and modern medicine. However, despite their importance, the complex biosynthetic pathways of many plant-derived compounds remain only partially understood, hindering their full potential in therapeutic applications. This review paper summarizes the advances in systems and synthetic biology utilized in the characterization and engineering of plant metabolic pathways. We discuss various strategies such as (1) co-expression analysis, (2) gene cluster identification, (3) metabolite profiling, (4) deep learning approaches, (5) genome-wide association studies, and (6) protein complex identification. Through case studies on several biosynthesis pathways, we highlight how these methods are applied to unravel complex pathways and enhance the production of important natural products. Finally, we discuss future directions in the context of metabolic engineering, including metabolon engineering, AI integration, and sustainable production strategies, underscoring the potential for cheaper and greener production of plant natural products.