title: Dual substrate-controlled kinase activity leads to polyphosphorylated lasso peptides.
abstract: Lasso peptides are characterized by their peculiar lariat knot-like structure. Except for maturation of this fold, post-translational modifications of lasso peptides are rare. However, we recently delineated the biosynthetic pathway of a post-translationally phosphorylated lasso peptide, paeninodin. In this study, further investigation of two kinases revealed their ability to transfer multiple phosphate groups onto precursor peptide substrates, ultimately leading to polyphosphorylated lasso peptides. We found that this polyphosphorylating activity depended on the identity of the phosphate donor and the sequence of the precursor peptide. Our investigations provide new insight into the remarkable strategies for chemical diversification employed by the lasso peptide biosynthetic machinery.
authors: Department of Chemistry and Biochemistry, Philipps-Universität Marburg, Germany.|State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, China.
authors: Shaozhou
authors: S
authors: Zhu
authors: Department of Chemistry and Biochemistry, Philipps-Universität Marburg, Germany.
authors: Christopher D
authors: CD
authors: Fage
authors: Department of Chemistry and Biochemistry, Philipps-Universität Marburg, Germany.
authors: Julian D
authors: JD
authors: Hegemann
authors: Department of Chemistry and Biochemistry, Philipps-Universität Marburg, Germany.
authors: Dushan
authors: D
authors: Yan
authors: Department of Chemistry and Biochemistry, Philipps-Universität Marburg, Germany. marahiel@staff.uni-marburg.de.
authors: Mohamed A
authors: MA
authors: Marahiel
mesh_terms: D001430:Bacteriocins / Q000737:chemistry* / Q000378:metabolism; D056507:Paenibacillus / Q000201:enzymology; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D043862:Rotaxanes / Q000737:chemistry* / Q000378:metabolism
chemical_list: C493079:BI-32169; D001430:Bacteriocins; D010455:Peptides; D010456:Peptides, Cyclic; D043862:Rotaxanes; C000593090:xanthomonin I; C020411:microcin; D011494:Protein Kinases
keywords: biosynthesis; kinase; lasso peptide; natural product; phosphorylation; post-translational modification