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Pyridoxal-5'-phosphate-dependent enzyme GenB3 Catalyzes C-3',4'-dideoxygenation in gentamicin biosynthesis.
- Source :
-
Microbial cell factories [Microb Cell Fact] 2021 Mar 09; Vol. 20 (1), pp. 65. Date of Electronic Publication: 2021 Mar 09. - Publication Year :
- 2021
-
Abstract
- Background: The C-3',4'-dideoxygenation structure in gentamicin can prevent deactivation by aminoglycoside 3'-phosphotransferase (APH(3')) in drug-resistant pathogens. However, the enzyme catalyzing the dideoxygenation step in the gentamicin biosynthesis pathway remains unknown.<br />Results: Here, we report that GenP catalyzes 3' phosphorylation of the gentamicin biosynthesis intermediates JI-20A, JI-20Ba, and JI-20B. We further demonstrate that the pyridoxal-5'-phosphate (PLP)-dependent enzyme GenB3 uses these phosphorylated substrates to form 3',4'-dideoxy-4',5'-ene-6'-oxo products. The following C-6'-transamination and the GenB4-catalyzed reduction of 4',5'-olefin lead to the formation of gentamicin C. To the best of our knowledge, GenB3 is the first PLP-dependent enzyme catalyzing dideoxygenation in aminoglycoside biosynthesis.<br />Conclusions: This discovery solves a long-standing puzzle in gentamicin biosynthesis and enriches our knowledge of the chemistry of PLP-dependent enzymes. Interestingly, these results demonstrate that to evade APH(3') deactivation by pathogens, the gentamicin producers evolved a smart strategy, which utilized their own APH(3') to activate hydroxyls as leaving groups for the 3',4'-dideoxygenation in gentamicin biosynthesis.
- Subjects :
- Anti-Bacterial Agents chemistry
Biocatalysis
Biosynthetic Pathways genetics
Gentamicins chemistry
Kanamycin Kinase metabolism
Micromonospora enzymology
Micromonospora genetics
Phosphorylation
Anti-Bacterial Agents biosynthesis
Anti-Bacterial Agents metabolism
Biosynthetic Pathways physiology
Gentamicins biosynthesis
Gentamicins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2859
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Microbial cell factories
- Publication Type :
- Academic Journal
- Accession number :
- 33750386
- Full Text :
- https://doi.org/10.1186/s12934-021-01558-7