{"doi":"10.1021/acs.biochem.6c00103","title":"Structure, Biosynthesis, and Bioactivity of Nostolysamides","abstract":null,"journal":"Biochemistry","year":2026,"id":669672,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1749021,"name":"Ivan Anterola","orcid":"0009-0002-5983-8943","position":1,"is_corresponding":false},{"id":256350,"name":"Wilfred A. van der Donk","orcid":"0000-0002-5467-7071","position":2,"is_corresponding":false},{"id":1749020,"name":"Enleyona Weir","orcid":"0000-0003-1744-3601","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structure, Biosynthesis, and Bioactivity of Nostolysamides","abstract":"A recent genome-mining study identified class II lanthipeptides encoded in Nostoc punctiforme PCC 73102 that contain acyl groups conjugated to Lys side chains. The structure and bioactivity of these peptides, named nostolysamides, were not determined. In this study, we produced the nostolysamides by coexpression of the NpuA precursor peptide with an N-terminal SUMO tag with the class II lanthipeptide synthetase NpuM in Escherichia coli . All four lanthionine and methyllanthionine residues were shown to have the DL configuration by Marfey’s analysis. Tandem mass spectrometry and mutagenesis studies indicate an N-terminal nonoverlapping methyllanthionine ring and three overlapping rings at the C-terminus, for which the most likely ring pattern is proposed. The NpuM lanthipeptide synthetase is a member of the ProcM-clade and catalyzes ring formation with both C-to-N and N-to-C directionality. After removal of the leader peptide, the resulting lanthipeptide exhibits antibacterial as well as antifungal activity against Candida species by disrupting cell membranes. Antibacterial activity is shown not to involve lipid II. The biosynthetic gene cluster also encodes an acetyltransferase NpuN that transfers long-chain acyl groups to the side chain of a Lys residue at position 1 of the precursor peptide. In vitro studies of NpuN show relatively broad substrate specificity, with NpuN conjugating various acyl groups from acyl-CoA substrates to Lys1 in the nostolysamides. The acylation did not appreciably change the antifungal and antimicrobial activity of nostolysamide, showing that it is not required for these activities.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42032808","pmcid":"PMC13142686","openalex_id":"https://openalex.org/W7155643082","authors":[],"funders":[{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"R01AI144967","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":2,"fwci":6.294,"citation_percentile":0.95527013,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"green","license":"https://doi.org/10.15223/policy-029","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13142686/","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13142686/","host_type":"repository"},{"url":"https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.6c00103","host_type":"publisher"},{"url":"https://doi.org/10.1021/acs.biochem.6c00103","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42032808","host_type":"repository"}],"fields_of_study":["Microbial Natural Products and Biosynthesis","Antimicrobial Peptides and Activities","Probiotics and Fermented Foods","Nostoc","Amino Acid Sequence","Anti-Bacterial Agents","Escherichia coli","Candida","Antifungal Agents","Molecular Sequence Data","Alanine","Sulfides"],"mesh_terms":["Alanine","Amino Acid Sequence","Anti-Bacterial Agents","Antifungal Agents","Bacterial Proteins","Bacteriocins","Candida","Escherichia coli","Ligases","Molecular Sequence Data","Sulfides","Nostoc"],"keywords":["Acylation","Residue (chemistry)","Side chain","Lanthionine","Peptide","Gene cluster","Ring (chemistry)","Mutagenesis","Acyl group"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T02:03:35.629389Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}