9Z8J

Gelatinamin A: a figure-of-eight lasso peptide

Summary for 9Z8J

• Entry DOI: 10.2210/pdb9z8j/pdb
• NMR Information: BMRB: 31284
• Descriptor: Gelatinamin A (1 entity in total)
• Functional Keywords: lasso peptide, antimycobacterial, mechanically interlocked peptide, antibiotic
• Biological source: Brevibacillus gelatini
• Total number of polymer chains: 1
• Total formula weight: 1786.13

Authors

Johnson, T.G.,Zhu, A.,Svenningsen, T.,Merrild, A.,Wang, F.,Andersen, F.D.,Iwase, R.,Viennet, T.,Larsen, M.K.,Link, A.J.,Torring, T. (deposition date: 2025-11-18, release date: 2026-05-27)

Primary citation

Svenningsen, T.,Merrild, A.,Wang, F.,Hansen, F.D.,Johnson, T.G.,Iwase, R.,Viennet, T.,Larsen, M.K.,Link, A.J.,Torring, T.
Biosynthesis, Structure, and Antibiotic Properties of Gelatinamin A, a Triculamin-Like Lasso Peptide.
Chembiochem, 27:e70378-e70378, 2026

PubMed Abstract: Lasso peptides are structurally unique natural products endowed with high thermal and proteolytic stability, making them attractive as scaffolds for drug discovery. Recently, a new class of lasso peptides containing a second macrocycle, formed between a lysine sidechain and the C-terminus, was discovered, resulting in an even more compact architecture. Here, we report the first NMR structure of the class V lasso peptide, gelatinamin A. Using heterologous expression of the gelatinamin biosynthetic gene cluster (BGC) in Bacillus subtilis, we delineated the biosynthetic pathway through targeted gene deletions. We expressed and characterized the predicted transpeptidase, GelP, that catalyzes the formation of an isopeptide bond between Lys2 and the C-terminus and mediates the reversible conversion of gelatinamin B to gelatinamin A. In addition, we characterize GelT, an N-acetyltransferase that inactivates lasso peptide antimicrobial activity by acetylating a key lysine residue. Furthermore, we demonstrate that gelatinamin is highly potent against several important pathogens and that the activity is strongly bicarbonate-dependent. Finally, we propose a complete biosynthetic pathway for gelatinamin. The structural insight of gelatinamin A and the functional characterization of GelP provide the foundation for future discovery of class V lasso peptides and for engineering transpeptidases to modify other lasso peptide scaffolds.

PubMed: 42138325
DOI: 10.1002/cbic.70378

Experimental method

SOLUTION NMR