Taming the hydra of specialized metabolism: how systems biology and comparative approaches are revolutionizing plant biochemistry.

Specialized (traditionally called 'secondary') metabolism can be thought of as a hydra with hundreds of thousands of compounds produced by thousands of enzymes across the entire plant kingdom. Until recently, plants that produce the most interesting and valuable metabolites were recalcitrant to modern molecular biology approaches for gene and pathway discovery. Recent advances in technologies for genomic, transcriptomic, proteomic, and metabolomic methods now allow for deployment of 'systems biology' approaches to help elucidate unknown steps in specialized metabolite pathways, for example through co-expression analyses. Inexpensive transcriptome and whole genome sequencing (WGS) promises to provide direct access to metabolic pathways in plants not currently used as reference organisms. For example, WGS has uncovered cases of physical proximity of genes of specialized metabolism. Further integration of multiple 'omics' datasets through advances in bioinformatics tools will increase our knowledge of pathway architecture and regulation at an ever-increasing rate. As such the era of systems biology is rapidly providing a broader and deeper understanding of plant specialized metabolism.