Engineering Microbes for Plant Polyketide Biosynthesis

Polyketides are an important group of secondary metabolites, many of which have important industrial applications in the food and pharmaceutical industries. Polyketides are synthesized from one of three classes of enzymes differentiated by their biochemical features and product structure: type I, type II or type III polyketide synthases (PKSs). Plant type III PKS enzymes, which will be the main focus of this review, are relatively small homodimeric proteins that catalyze iterative decarboxylative condensations of malonyl units with a CoA-linked starter molecule. This review will describe the plant type III polyketide synthetic pathway, including the synthesis of chalcones, stilbenes and curcuminoids, as well as recent work on the synthesis of these polyketides in heterologous organisms. The limitations and bottlenecks of heterologous expression as well as attempts at creating diversity through the synthesis of novel “unnatural” polyketides using type III PKSs will also be discussed. Although synthetic production of plant polyketides is still in its infancy, their potential as useful bioactive compounds makes them an extremely interesting area of study.