{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:44:40Z","timestamp":1785433480239,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,31]]},"group-title":"Biochemistry","reference-count":104,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 AI144967"],"award-info":[{"award-number":["R01 AI144967"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A recent genome mining study identified class II lanthipeptides encoded in\n                  <jats:italic>Nostoc punctiforme<\/jats:italic>\n                  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 co-expression of the NpuA precursor peptide with an N-terminal SUMO tag with the class II lanthipeptide synthetase NpuM in\n                  <jats:italic>Escherichia coli.<\/jats:italic>\n                  All four lanthionine and methyllanthionine residues were shown to have the DL configuration by Marfey\u2019s analysis. Tandem mass spectrometry and mutagenesis studies indicate an N-terminal non-overlapping 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\n                  <jats:italic>Candida<\/jats:italic>\n                  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 in position 1 of the precursor peptide.\n                  <jats:italic>In vitro<\/jats:italic>\n                  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.\n                <\/jats:p>","DOI":"10.64898\/2026.01.31.703028","type":"posted-content","created":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T04:40:12Z","timestamp":1769920812000},"source":"Crossref","is-referenced-by-count":0,"title":["Structure, biosynthesis, and bioactivity of nostolysamides"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-3601","authenticated-orcid":false,"given":"Enleyona","family":"Weir","sequence":"first","affiliation":[{"name":"Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL, 61822, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5983-8943","authenticated-orcid":false,"given":"Ivan","family":"Anterola","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL, 61822, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-7071","authenticated-orcid":false,"given":"Wilfred A.","family":"van der Donk","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL, 61822, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040802200560000_2026.01.31.703028v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00692-8"},{"key":"2026040802200560000_2026.01.31.703028v2.2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.045054-0"},{"key":"2026040802200560000_2026.01.31.703028v2.3","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1021\/acsinfecdis.5c00079","article-title":"Candida albicans: insights into the biology and experimental innovations of a commonly isolated human fungal pathogen","volume":"11","year":"2025","journal-title":"ACS Infect. 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