Pyridoxal-5'-phosphate-dependent enzyme GenB3 Catalyzes C-3',4'-dideoxygenation in gentamicin biosynthesis.
Microb Cell Fact
; 20(1): 65, 2021 Mar 09.
Article
em En
| MEDLINE
| ID: mdl-33750386
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.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.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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gentamicinas
/
Vias Biossintéticas
/
Antibacterianos
Idioma:
En
Revista:
Microb Cell Fact
Assunto da revista:
BIOTECNOLOGIA
/
MICROBIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China