(4ce) Discovery and Characterization of the Astexin Family of Lasso Peptides

Genome mining has empowered the rational discovery of novel natural products in the post-genomic era.  Motivated by the unique chemical properties of lasso peptides such as their extraordinary stability and natural antimicrobial activity, we set out to develop a novel genome-mining algorithm tailored to their unique characteristics.  Our results identified 79 putative lasso peptide biosynthesis clusters and were validated by the expression and characterization of a novel member of the class called astexin-1 (1).  We have continued our work in this direction by characterizing two peptides encoded by the same organism called astexin-2 and astexin-3.  As a result of our work and efforts in other laboratories, the number of confirmed lasso peptides has nearly doubled in the past two years.  The expansion in information about the lasso peptide family led us to reexamine the gene architectures of this class of natural products.  Through this line of inquiry, we were able to characterize a new enzyme involved in lasso peptide biosynthesis and glean valuable insights about the evolution of this peptide class. 

1. Maksimov MO, Pelczer I, & Link AJ (2012) Precursor-centric genome-mining approach for lasso peptide discovery. Proceedings of the National Academy of Sciences 109(38):15223-15228.