Summary: | Influencing the production of natural products in planta by metabolic engineering approaches has become an increasingly popular means to address a variety of important agricultural, medicinal, and nutraceutical issues. There have been many successes in this area, but also many surprising and unanticipated results. As an understanding of the complexity of metabolism has emerged, it has become increasingly apparent that successfully designing synthetic approaches to influence metabolite production requires knowledge beyond that of just the individual enzymatic steps involved and the order in which they are arranged into a biosynthetic pathway. Although much remains to be learned about the structures of metabolic organization and their impact on flux in living systems, taking the information that is available into account is one step towards helping to overcome the difficulties in generating sufficient yields of current natural products of interest and to accelerate the production of target compounds in the future. In this review, we reflect on current knowledge relating to the use of metabolic engineering of plant natural product pathways to influence the production of compounds of interest and consider the impact that higher levels of organization, such as metabolon formation, may have on these systems.
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