Subcellular compartmentalization in the biosynthesis and engineering of plant natural products

Plant natural products (PNPs) are specialized metabolites with diverse bioactivities. They are extensively used in the pharmaceutical, cosmeceutical and food industries. PNPs are synthesized in plant cells by enzymes that are distributed in different subcellular compartments with unique microenvironments, such as ions, co-factors and substrates. Plant metabolic engineering is an emerging and promising approach for the sustainable production of PNPs, for which the knowledge of the subcellular compartmentalization of their biosynthesis is instrumental. In this review we describe the state of the art on the role of subcellular compartments in the biosynthesis of major types of PNPs, including terpenoids, phenylpropanoids, alkaloids and glucosinolates, and highlight the efforts to target biosynthetic pathways to subcellular compartments in plants. In addition, we will discuss the challenges and strategies in the field of plant synthetic biology and subcellular engineering. We expect that newly developed methods and tools, together with the knowledge gained from the microbial chassis, will greatly advance plant metabolic engineering.