The Astexin-1 Lasso Peptides: Biosynthesis, Stability, and Structural Studies

•Investigation of thermal and proteolytic stability of astexin-1(19) and astexin-1(23)•Mutational study of astexin-1 including alanine scan and truncations•NMR spectroscopic study of astexin-1(19) and (23) and NMR structure of astexin-1(19)•Creation of the heat-stabile variant astexin-1(19) F15W

SummaryLasso peptides are a large family of natural products that owe their name to a unique structure formed by a side chain to backbone macrocyclization, resembling a knotted lasso. The unique structure has significant impact on their biological and physical properties, as lasso peptides are usually more stable than linear ones. Current work examines stability, structure, and biosynthesis of recently discovered lasso peptide astexin-1, a heat-sensitive lasso peptide. The obtained results revealed a new lasso structure with a tight loop and long tail as well as narrow specificity of the maturation machinery for some essential residues associated with the protease processing site, involved in macrolactam ring formation and entrapment of the tail. Using the astexin-1 structure, it was possible to rationally construct a thermostable variant of this lasso peptide.

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