Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides
Glycopeptide antibiotics are valuable natural metabolites endowed with different pharmacological properties, among them are dalbaheptides used to treat different infections caused by multidrug-resistant Gram-positive pathogens. Dalbaheptides are produced by soil-dwelling high G-C Gram-positive actin...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.858708/full |
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| author | Oleksandr Yushchuk Oleksandr Yushchuk Kseniia Zhukrovska Francesca Berini Victor Fedorenko Flavia Marinelli |
| author_facet | Oleksandr Yushchuk Oleksandr Yushchuk Kseniia Zhukrovska Francesca Berini Victor Fedorenko Flavia Marinelli |
| author_sort | Oleksandr Yushchuk |
| collection | DOAJ |
| description | Glycopeptide antibiotics are valuable natural metabolites endowed with different pharmacological properties, among them are dalbaheptides used to treat different infections caused by multidrug-resistant Gram-positive pathogens. Dalbaheptides are produced by soil-dwelling high G-C Gram-positive actinobacteria. Their biosynthetic pathways are encoded within large biosynthetic gene clusters. A non-ribosomally synthesized heptapeptide aglycone is the common scaffold for all dalbaheptides. Different enzymatic tailoring steps, including glycosylation, are further involved in decorating it. Glycosylation of dalbaheptides is a crucial step, conferring them specific biological activities. It is achieved by a plethora of glycosyltransferases, encoded within the corresponding biosynthetic gene clusters, able to install different sugar residues. These sugars might originate from the primary metabolism, or, alternatively, their biosynthesis might be encoded within the biosynthetic gene clusters. Already installed monosaccharides might be further enzymatically modified or work as substrates for additional glycosylation. In the current minireview, we cover recent updates concerning the genetics and enzymology behind the glycosylation of dalbaheptides, building a detailed and consecutive picture of this process and of its biological evolution. A thorough understanding of how glycosyltransferases function in dalbaheptide biosynthesis might open new ways to use them in chemo-enzymatic synthesis and/or in combinatorial biosynthesis for building novel glycosylated antibiotics. |
| first_indexed | 2024-12-13T08:19:21Z |
| format | Article |
| id | doaj.art-d7d8008f615d4a4e80deeb9d1b4fcf9d |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-13T08:19:21Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-d7d8008f615d4a4e80deeb9d1b4fcf9d2022-12-21T23:54:03ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-03-011010.3389/fchem.2022.858708858708Genetics Behind the Glycosylation Patterns in the Biosynthesis of DalbaheptidesOleksandr Yushchuk0Oleksandr Yushchuk1Kseniia Zhukrovska2Francesca Berini3Victor Fedorenko4Flavia Marinelli5Department of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, Lviv, UkraineDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, Lviv, UkraineDepartment of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyDepartment of Genetics and Biotechnology, Ivan Franko National University of Lviv, Lviv, UkraineDepartment of Biotechnology and Life Sciences, University of Insubria, Varese, ItalyGlycopeptide antibiotics are valuable natural metabolites endowed with different pharmacological properties, among them are dalbaheptides used to treat different infections caused by multidrug-resistant Gram-positive pathogens. Dalbaheptides are produced by soil-dwelling high G-C Gram-positive actinobacteria. Their biosynthetic pathways are encoded within large biosynthetic gene clusters. A non-ribosomally synthesized heptapeptide aglycone is the common scaffold for all dalbaheptides. Different enzymatic tailoring steps, including glycosylation, are further involved in decorating it. Glycosylation of dalbaheptides is a crucial step, conferring them specific biological activities. It is achieved by a plethora of glycosyltransferases, encoded within the corresponding biosynthetic gene clusters, able to install different sugar residues. These sugars might originate from the primary metabolism, or, alternatively, their biosynthesis might be encoded within the biosynthetic gene clusters. Already installed monosaccharides might be further enzymatically modified or work as substrates for additional glycosylation. In the current minireview, we cover recent updates concerning the genetics and enzymology behind the glycosylation of dalbaheptides, building a detailed and consecutive picture of this process and of its biological evolution. A thorough understanding of how glycosyltransferases function in dalbaheptide biosynthesis might open new ways to use them in chemo-enzymatic synthesis and/or in combinatorial biosynthesis for building novel glycosylated antibiotics.https://www.frontiersin.org/articles/10.3389/fchem.2022.858708/fullglycopeptide antibioticsdalbaheptidesramoplaninteicoplaninA40926glycosyltransferase |
| spellingShingle | Oleksandr Yushchuk Oleksandr Yushchuk Kseniia Zhukrovska Francesca Berini Victor Fedorenko Flavia Marinelli Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides Frontiers in Chemistry glycopeptide antibiotics dalbaheptides ramoplanin teicoplanin A40926 glycosyltransferase |
| title | Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides |
| title_full | Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides |
| title_fullStr | Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides |
| title_full_unstemmed | Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides |
| title_short | Genetics Behind the Glycosylation Patterns in the Biosynthesis of Dalbaheptides |
| title_sort | genetics behind the glycosylation patterns in the biosynthesis of dalbaheptides |
| topic | glycopeptide antibiotics dalbaheptides ramoplanin teicoplanin A40926 glycosyltransferase |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.858708/full |
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