Opportunities for enzyme engineering in natural product biosynthesis

Organisms from all kingdoms of life produce a plethora of natural products that display a range of biological activities. One key limitation of developing these natural products into pharmaceuticals is the inability to perform effective, fast, and inexpensive structure–activity relationship studies (SAR). Recently, enzyme engineering strategies have allowed the exploration of metabolic engineering of biosynthetic pathways to create new ‘natural’ products that can be used for SAR. The enzymes that enable the biosynthesis of natural products represent a largely untapped resource of potential biocatalysts. A challenge for the field is how to harness the wealth of reaction types used for natural product metabolism to obtain useful biocatalysts for industrial biotransformations.