How to harness biosynthetic gene clusters of lasso peptides
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NATURAL PRODUCTS - MINI REVIEW
How to harness biosynthetic gene clusters of lasso peptides Shinya Kodani1,2 · Kohta Unno2 Received: 4 May 2020 / Accepted: 14 July 2020 © Society for Industrial Microbiology and Biotechnology 2020
Abstract Lasso peptides produced by bacteria have a very unique cyclic structure (“lasso” structure) and are resistant to protease. To date, a number of lasso peptides have been isolated from proteobacteria and actinobacteria. Many lasso peptides exhibit various biological activities, such as antibacterial activity, and are expected to have various applications. Based on study of genome mining, large numbers of biosynthetic gene cluster of lasso peptides are revealed to distribute over genomes of proteobacteria and actinobacteria. However, the biosynthetic gene clusters are cryptic in most cases. Therefore, the combination of genome mining and heterologous production is efficient method for the production of lasso peptides. To utilize lasso peptide as fine chemical, there have been several attempts to add new function to lasso peptide by genetic engineering. Currently, a more efficient lasso peptide production system is being developed to harness cryptic biosynthetic gene clusters of lasso peptide. In this review, the overview of lasso peptide study is discussed.
Introduction In recent years, medium-sized molecules have attracted attention as candidate molecules for drug development. Small molecule drugs can be administered orally and have low immunotoxicity, but these drugs may cause side effects due to their low specificity. On the other hand, high molecular weight protein drugs have high specificity and few side effects, but their application range is narrow, and there is a problem of immunotoxicity. Peptides with medium sizes (0.5–5 kDa) are expected to have the advantages of both molecules. Naturally occurring peptides derived from bacteria are attractive sources for medium-sized molecules. Among bacterial peptides, “lasso peptides” are very promising compounds due to its structural varieties with biological activities [11, 36, 68, 69]. Lasso peptides are a group of peptides named after “lasso” (a rope with a noose at one end). This class of peptides has been reported from bacteria, including proteobacteria and actinobacteria. Lasso peptide is comprised of 14–33 amino acids in length and possesses a slipknot structure as a motif at the N-terminus. In the lasso * Shinya Kodani [email protected] 1
College of Agriculture, Academic Institute, Shizuoka University, 836 Ohya, Suruga‑ku, Shizuoka 422‑8529, Japan
Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422‑8529, Japan
2
peptide molecule, an isopeptide bond is present between the amino group of the N-terminal amino acid and the β- or γ-carboxyl group of Asp or Glu at the 7th–9th position from the N-terminus, forming a macrolactam ring. The lasso peptide microcin J25 was isolated from Escherichia coli, and it is regarded as the archetype of lasso peptides [1, 5, 90, 94, 104]. I
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