Current and Emerging Approaches for Natural Product Biosynthesis in Microbial Cells

Abstract

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.

Biosynthesis of Ubiquinone Compounds with Conjugated Prenyl Side Chains

“…Many of these mechanisms, like the evolution of new protein functions and combination of genes from related pathways into new biosynthetic reaction sequences, have been adapted as laboratory approaches to direct the biosynthesis of novel metabolites (17,24,25,30,33,34,48). There are, however, few examples of separate biosynthetic pathways being combined in engineered cells to generate new classes of natural products.…”

Application of Functional Genomics to Pathway Optimization for Increased Isoprenoid Production

“…Production of chemicals via synthetic enzymatic pathways in heterologous hosts has proven useful for many important classes of molecules, including isoprenoids (61), polyketides (49,50), nonribosomal peptides (61), bioplastics (1), and chemical building blocks (45). Due to the inherent modularity of biological information, synthetic biology holds great potential for expanding this list of microbially produced compounds even further.…”

Anchoring high-throughput screening methods to scale-up bioproduction of siderophores

“…therapeutic steroids [1], biofuels [2] and terpenoids [3]. The combination of the natural diversity with further synthetic modifications provides an unlimited resource for complex compounds unmatched by chemical synthesis [4,5].…”