Characterization of caulonodin lasso peptides revealed unprecedented N-terminal residues and a precursor motif essential for peptide maturation

Abstract

We report four new class II lasso peptides featuring alanine and serine at position 1, a bioinformatically identified leader motif and its mutational analysis revealing significant impact on precursor processing.

Dual substrate‐controlled kinase activity leads to polyphosphorylated lasso peptides

“…3A, ThcoK transferred up to three phosphate groups onto S-ThcoA (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) when ATP served as the phosphate donor; however, a singly phosphorylated peptide appeared as the main product. Conversely, when ATP was replaced with GTP, singly and doubly phosphorylated peptides were produced in nearly equal amounts.…”

“…Extensive post-translational modifications enrich the structural diversity and, thereby, chemical stability and bioactivity of such compounds. Lasso peptides are members of an intriguing family of RiPPs that possess an unusual lariat knot-like structure [6][7][8][9][10][11][12][13][14]: the N terminus of the peptide is covalently cyclized with an acidic side chain to form a 7-, 8-, or 9-residue macrolactam ring; the C terminus is threaded through this ring and trapped by bulky side chains, thus stabilizing the entropically disfavored conformation (Fig. 1A) [9][10][11]13,[15][16][17][18][19][20][21][22][23][24].…”

Insights into the Unique Phosphorylation of the Lasso Peptide Paeninodin

“…Generally, all known lasso peptides carry a Gly, Ala, Cys, or Ser residue at position 1 and a ring-forming Glu or Asp residue at positions 7-9 (3,4,7,10,11,21,25). Their respective processing enzymes are highly specific for the nature and location of these residues (6, 9 -11, 16, 28 -30).…”

Natural product diversity of actinobacteria in the Atacama Desert

“…Lasso peptides (LPs) are a rare class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that feature a unique "lariat knot" structural motif (Zimmermann et al 2014;Arnison et al 2013). The post-translational modification includes an isopeptide bond forming a 7-9 amino acid N-terminal macrolactam ring through which the remaining Cterminal chain is threaded (Zimmermann et al 2014).…”

“…The post-translational modification includes an isopeptide bond forming a 7-9 amino acid N-terminal macrolactam ring through which the remaining Cterminal chain is threaded (Zimmermann et al 2014). LPs are classified into three sub-classes based on their N-terminal residues and the number of disulfide bridges.…”