Genome mining for lasso peptides: past, present, and future

Area of Science:

• Biochemistry and Molecular Biology
• Genomics
• Natural Product Discovery

Background:

• Lasso peptides are a unique class of cyclic peptides with a topologically complex structure.
• Historically, discovery relied on traditional bioactivity screening, yielding few new compounds.
• The advent of genomics has opened new avenues for natural product discovery.

Purpose of the Study:

• To provide a historical overview of lasso peptide discovery methods.
• To highlight the impact and evolution of genome-mining approaches for lasso peptide identification.
• To discuss novel lasso peptides, associated enzymes, and future research directions in the field.

Main Methods:

• Review of historical activity-driven discovery approaches.
• Analysis of early and modern genome-mining strategies for lasso peptide identification.
• Examination of associated enzymes within lasso peptide gene clusters.

Main Results:

• Genome mining is now the predominant method for lasso peptide discovery.
• Numerous novel lasso peptides have been identified through genomic approaches.
• New enzymes linked to lasso peptide biosynthesis have been discovered.

Conclusions:

• Genome mining has transformed the landscape of lasso peptide research.
• Continued development of genome-mining tools will accelerate the discovery of novel lasso peptides and related enzymes.
• Addressing current challenges in genome mining is crucial for future advancements.