Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria
| العنوان: | Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria |
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| المؤلفون: | Joyce Liu, Jordan Downey, Ryan Khalaf, Nicolaus A. Herman, Michio Sato, Hiroyuki Koshino, Wenlong Cai, Frederick F. Twigg, Xuejun Zhu, Joelle Martin, Nicholas C. Harris, Wenjun Zhang |
| المصدر: | Proceedings of the National Academy of Sciences. 114:7025-7030 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Catalysis, Condensation domain, Acylation, Lipopeptides, 03 medical and health sciences, chemistry.chemical_compound, Protein Domains, Thioesterase, Biosynthesis, Nonribosomal peptide, Gene cluster, Escherichia coli, Peptide Synthases, Gene, chemistry.chemical_classification, Chromatography, Multidisciplinary, Chemistry, Lysine, Fatty Acids, Lipopeptide, Biological Transport, Mycobacterium tuberculosis, Biological Sciences, Chromatography, Ion Exchange, Actinobacteria, 030104 developmental biology, Biochemistry, Metals, Multigene Family, Mutation, Mycobacterium marinum, Ribosomes, Gene Deletion |
| الوصف: | A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase. In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1faf4c81d0d5020bb4eb67a3ed6ab672Test https://doi.org/10.1073/pnas.1705016114Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1faf4c81d0d5020bb4eb67a3ed6ab672 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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