Synthetic and systems biology strategies for enhanced plant secondary metabolite production

From their initial discovery in plants to later identification in bacteria and fungi, secondary metabolites such as phenolics, alkaloids, terpenoids, and flavonoids have remained a central focus of metabolomics research. Their bioactive properties attract pharmaceutical, food, and allied industries due to diverse functionalities and significant revenue potential. Early studies prioritized basic chemistry, extraction, and structural elucidation, but contemporary insights into secondary metabolite production stem from analyzing their biosynthetic pathways and gene families. Advances in omics-based approaches now aim to enhance yields cost-effectively. Recent developments in sustainable agriculture highlight the integration of synthetic biology with plant systems biology, improving genetic engineering precision to boost secondary metabolite synthesis. CRISPR-Cas and gene-editing platforms enable the design of synthetic promoters, regulatory elements, and gene circuits. These tools, coupled with environmental modulation, allow targeted pathway manipulation. However, the complexity of plant metabolic networks and incomplete understanding of their regulation hinder large-scale implementation. A key challenge lies in determining the optimal approaches for each target metabolite in terms of methodology, timing, and specificity. This review critically evaluates recent advances in synthetic and systems biology for regulating plant secondary metabolism. It also explores how these tools elucidate new biosynthetic genes, reveal metabolic clusters, and propose strategies to optimize production.