Lasso peptide, a family of ribosomally synthesized and posttranslationally modified peptides (RiPPs), has remarkable thermal and proteolytic stability and a wide range of bioactivities, including antimicrobial activity, enzyme inhibition, receptor blocking, anticancer properties, and HIV antagonism. They may be suitable for drug development and could prove beneficial in gastrointestinal diseases, tuberculosis, Alzheimer’s disease, cardiovascular disease, fungal infections, and cancer.
Lasso peptide is produced by bacteria and has a macrocyclic ring, which is formed by seven to nine N-terminal amino acid residues. This interlocked topology is unique among the RiPPs and confers lasso peptides high thermal and proteolytic stability.
The structural and biological characterization of lasso peptides has become increasingly important because of their remarkable thermal and proteolytic stability, as well as the wide range of biological activities they exhibit. Moreover, these peptides are good carriers for other bioactive molecules, thereby enhancing their therapeutic potential.
Chemical synthesis of lasso peptide is extremely challenging, due to the difficulty of identifying and extracting peptide precursors from native producers and the high turnover rate of the biosynthetic pathways in these organisms. However, recent studies have shown that segments of lasso peptides can be incorporated into proteins, thereby generating fusions. In addition, these peptides have been used as drug leads by combining the lasso peptides with other bioactive peptides in an acetylated form to enhance their activity and/or stability.
To overcome these limitations, a variety of recombinant genetics have been used to produce lasso peptides in different host bacteria. For example, citrulassin A originating from S albus DSM 41398 was heterologously expressed in Streptomyces lividans and Brevundimonas diminuta under optimized culture conditions. Heterologous expression of other lasso peptides was achieved through the use of yeast- or phage-display systems.