Current and emerging approaches for natural product biosynthesis in microbial cells

Microorganisms and plants synthesize a tremendous diversity of chemical compounds. For centuries, these compounds have been used as medicines, foods and other useful materials. The still largely unexplored structural and chemical diversity of natural products is unmatched by synthetic methodology and continues to be the most successful source for the discovery of novel scaffolds with important biological activities. Thus, exploiting the selectivity and specificity of the biosynthetic machineries that make these complex compounds can provide ways of synthesizing diverse natural products or their core scaffolds for further synthetic modification. Microbial cells can be fitted with new biosynthetic abilities using metabolic and genetic engineering strategies to overproduce desired compounds. Efforts in genome sequencing give access to an incredible number of genes from microorganisms and, more recently, from plants that can be in silico screened for new biosynthetic functions allowing tapping into the synthetic potential of microorganisms, and especially plants. In addition, by exploiting natural biodiversity by using traditional screening methods or metagenomics approaches, novel biosynthetic pathways and genes can be discovered for the synthesis of additional structures in engineered microbial cells. In this review, we will describe some of the recent developments in natural product biosynthesis, and also describe some of the emerging approaches to harness the chemical diversity that lies hidden in nature.