Bioinformatics-guided discovery of biaryl-linked lasso peptides.

Autor:	Saad H; Department of Pharmaceutical Biology, Institute of Pharmaceutical Sciences, University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany hamada.saad@pharm.uni-tuebingen.de harald.gross@uni-tuebingen.de.; Department of Chemistry and the Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign Urbana Illinois 61801 USA., Majer T; Department of Pharmaceutical Biology, Institute of Pharmaceutical Sciences, University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany hamada.saad@pharm.uni-tuebingen.de harald.gross@uni-tuebingen.de., Bhattarai K; Department of Pharmaceutical Biology, Institute of Pharmaceutical Sciences, University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany hamada.saad@pharm.uni-tuebingen.de harald.gross@uni-tuebingen.de., Lampe S; Department of Pharmaceutical Biology, Institute of Pharmaceutical Sciences, University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany hamada.saad@pharm.uni-tuebingen.de harald.gross@uni-tuebingen.de., Nguyen DT; Department of Chemistry and the Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign Urbana Illinois 61801 USA., Kramer M; Institute of Organic Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany., Straetener J; Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen Auf der Morgenstelle 28 72076 Tübingen Germany., Brötz-Oesterhelt H; Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen Auf der Morgenstelle 28 72076 Tübingen Germany.; Cluster of Excellence: EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen Tübingen Germany., Mitchell DA; Department of Chemistry and the Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign Urbana Illinois 61801 USA., Gross H; Department of Pharmaceutical Biology, Institute of Pharmaceutical Sciences, University of Tübingen Auf der Morgenstelle 8 72076 Tübingen Germany hamada.saad@pharm.uni-tuebingen.de harald.gross@uni-tuebingen.de.; Cluster of Excellence: EXC 2124: Controlling Microbes to Fight Infection, University of Tübingen Tübingen Germany.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2023 Oct 30; Vol. 14 (45), pp. 13176-13183. Date of Electronic Publication: 2023 Oct 30 (Print Publication: 2023).
DOI:	10.1039/d3sc02380j
Abstrakt:	Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that feature an isopeptide bond and a distinct lariat fold. A growing number of secondary modifications have been described that further decorate lasso peptide scaffolds. Using genome mining, we have discovered a pair of lasso peptide biosynthetic gene clusters (BGCs) that include cytochrome P450 genes. Using mass spectrometry, stable isotope incorporation, and extensive 2D-NMR spectrometry, we report the structural characterization of two unique examples of (C-N) biaryl-linked lasso peptides. Nocapeptin A, from Nocardia terpenica , is tailored with a Trp-Tyr crosslink, while longipepetin A, from Longimycelium tulufanense , features a Trp-Trp linkage. Besides the unusual bicyclic frame, a Met of longipepetin A undergoes S -methylation to yield a trivalent sulfonium, a heretofore unprecedented RiPP modification. A bioinformatic survey revealed additional lasso peptide BGCs containing P450 enzymes which await future characterization. Lastly, nocapeptin A bioactivity was assessed against a panel of human and bacterial cell lines with modest growth-suppression activity detected towards Micrococcus luteus . Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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