Structural insights into the diverse prenylating capabilities of DMATS prenyltransferases

Covering: 2009 up to August 2023Prenyltransferases (PTs) are involved in the primary and the secondary metabolism of plants, bacteria, and fungi, and they are key enzymes in the biosynthesis of many clinically relevant natural products (NPs). The continued biochemical and structural characterization of the soluble dimethylallyl tryptophan synthase (DMATS) PTs over the past two decades have revealed the significant promise that these enzymes hold as biocatalysts for the chemoenzymatic synthesis of novel drug leads. This is a comprehensive review of DMATSs describing the structure-function relationships that have shaped the mechanistic underpinnings of these enzymes, as well as the application of this knowledge to the engineering of DMATSs. We summarize the key findings and lessons learned from these studies over the past 14 years (2009-2023). In addition, we identify current gaps in our understanding of these fascinating enzymes. This review unpacks the accumulated knowledge of the structural bases of the unique properties and capabilities of DMATS-type prenyltransferases (PTs) that make them promising biocatalysts.

Automated summary

This review provides a comprehensive overview of dimethylallyl tryptophan synthase (DMATS) prenyltransferases (PTs), covering their structure-function relationships, engineering applications, and mechanistic understanding. It summarizes key findings and lessons learned from studies conducted over the past 14 years (2009-2023), while also identifying current gaps in our knowledge about these enzymes. The review highlights the accumulated knowledge about the unique properties and capabilities of DMATS-type PTs as promising biocatalysts.