43CP

Aphotorhaptin A, N-acetylated monocyclic daropeptide from Photorhabdus asymbiotica

Summary for 43CP

• Entry DOI: 10.2210/pdb43cp/pdb
• Descriptor: ACE-GLN-UN8-THR-PHE-ARG-PHE (1 entity in total)
• Functional Keywords: ribosomal peptide, ether crosslink, cyclophane, acetylation, unknown function
• Biological source: Photorhabdus asymbiotica
• Total number of polymer chains: 1
• Total formula weight: 927.04

Authors

Ma, S.,Liu, Z.,Zhang, Q. (deposition date: 2026-06-26, release date: 2026-08-05, Last modification date: 2026-08-12)

Primary citation

Ma, S.,Li, R.,Gao, X.,Gemmell, E.,Guo, S.,Chen, H.,Huang, X.,Capper, M.,Liu, Z.,Deng, Z.,Ding, W.,Kohnke, J.,Wang, X.,Zhang, Q.
An N-acetylated daropeptide modulates nematode development.
Proc.Natl.Acad.Sci.USA, 123:e2617449123-e2617449123, 2026

PubMed Abstract: The symbiotic bacterium is a rich source of bioactive secondary metabolites that mediate tripartite interactions with nematodes and insect hosts. However, natural products of ribosomal origin remain largely underexplored within this ecological niche. Here, we report the identification of aphotorhaptin A, a darobactin-like peptide (daropeptide) natural product from , which structurally features an ether crosslink and an N-terminal acetyl unit. Biosynthetic investigation uncovers aphotorhaptin A is matured via an unexpected leader cleavage step, and the subsequent N-terminal acetylation confers metabolic stability that maintains the hexapeptide scaffold integrity. Biochemical and structural studies demonstrate the acetyltransferase PasC exhibits remarkable substrate promiscuity, facilitated by an expansive active-site cavity that accommodates diverse acyl-CoA donors and peptide substrates. Unlike the antimicrobial darobactin, aphotorhaptin A appears to lack antibacterial activity but modulates nematode development, and this activity requires the ether crosslink and the N-terminal acetyl group in the hexapeptide scaffold. These findings expand the chemical and biosynthetic space of ribosomal peptide family and establish its link with nematode development and reproduction.

PubMed: 42555644
DOI: 10.1073/pnas.2617449123

Experimental method

SOLUTION NMR