| Autor: |
Gorkha Raj Giri, Priti Saxena |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 17, Iss 1 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| Popis: |
O-methylation of small molecules is a common modification widely present in most organisms. Type III polyketides undergo O-methylation at hydroxyl end to play a wide spectrum of roles in bacteria, plants, algae, and fungi. Mycobacterium marinum harbours a distinctive genomic cluster with a type III pks gene and genes for several polyketide modifiers including a methyltransferase gene, mmar_2193. This study reports functional analyses of MMAR_2193 and reveals multi-methylating potential of the protein. Comparative sequence analyses revealed conservation of catalytically important motifs in MMAR_2193 protein. Homology-based structure-function and molecular docking studies suggested type III polyketide cores as possible substrates for MMAR_2193 catalysis. In vitro enzymatic characterization revealed the capability of MMAR_2193 protein to utilize diverse polyphenolic substrates to methylate several hydroxyl positions on a single substrate molecule. High-resolution mass spectrometric analyses identified multi-methylations of type III polyketides in cell-free reconstitution assays. Notably, our metabolomics analyses identified some of these methylated molecules in biofilms of wild type Mycobacterium marinum. This study characterizes a novel mycobacterial O-methyltransferase protein with multi-methylating enzymatic ability that could be exploited to generate a palette of structurally distinct bioactive molecules. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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