Ribosomally Synthesized and Post-Translationally Modified Peptides Assembled by ThiF-like Adenylyltransferases: Recent Advances and Future Perspectives

TL;DR

This review explores enzymes involved in making unique peptides and highlights gaps in understanding their roles and potential for new discoveries.

Contribution

The paper provides a critical review of recent advances in understanding the TLAT enzyme superfamily and RiPP biosynthesis.

Findings

TLATs are found in many uncharacterized RiPP biosynthetic pathways.

There are significant gaps in understanding the catalytic potential of TLATs.

Recent insights into RiPP gene clusters and their enzymatic functions are discussed.

Abstract

Advances in whole genome sequencing have transformed GenBank into a veritable goldmine of uncharacterized and predicted proteins, many of which still await functional characterization. Notably, natural product biosynthetic pathways are often organized in gene clusters, unlocking thrilling avenues for the discovery of novel metabolites and distinctive enzymatic reactions. In this review, we focus on the versatile ThiF-like adenylyltransferase superfamily (TLATs), a group of enzymes essential for the biosynthesis of a diverse array of ribosomally synthesized and post-translationally modified peptides (RiPPs). Recent researches have revealed that TLATs are widespread in numerous yet uncharacterized RiPP biosynthetic pathways, highlighting significant gaps in our understanding of their extensive catalytic potential. Here, we critically review the latest insights into RiPP gene clusters containing these enzymes, discussing the natural products they generate, their enzymatic functions, catalytic mechanisms, and promising directions for future research.

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