The bifunctional enzyme, GenB4, catalyzes the last step of gentamicin 3',4'-di-deoxygenation via reduction and transamination activities

Microbial Cell Factories
Xiaotang ChenHuanzhang Xia

Abstract

New semi-synthetic aminoglycoside antibiotics generally use chemical modifications to avoid inactivity from pathogens. One of the most used modifications is 3',4'-di-deoxygenation, which imitates the structure of gentamicin. However, the mechanism of di-deoxygenation has not been clearly elucidated. Here, we report that the bifunctional enzyme, GenB4, catalyzes the last step of gentamicin 3',4'-di-deoxygenation via reduction and transamination activities. Following disruption of genB4 in wild-type M. echinospora, its products accumulated in 6'-deamino-6'-oxoverdamicin (1), verdamicin C2a (2), and its epimer, verdamicin C2 (3). Following disruption of genB4 in M. echinospora ΔgenK, its products accumulated in sisomicin (4) and 6'-N-methylsisomicin (5, G-52). Following in vitro catalytic reactions, GenB4 transformed sisomicin (4) to gentamicin C1a (9) and transformed verdamicin C2a (2) and its epimer, verdamicin C2 (3), to gentamicin C2a (11) and gentamicin C2 (12), respectively. This finding indicated that in addition to its transamination activity, GenB4 exhibits specific 4',5' double-bond reducing activity and is responsible for the last step of gentamicin 3',4'-di-deoxygenation. Taken together, we propose three new intermedia...Continue Reading

References

May 1, 1976·The Journal of Antibiotics·J A MarquezM J Weinstein
Oct 1, 1987·Journal of Clinical Pharmacy and Therapeutics·A Mathews, G R Bailie
Jun 6, 2008·Biochemical and Biophysical Research Communications·Jin-Yong KimHyung-Jin Kwon
Sep 14, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Maria S Ramirez, Marcelo E Tolmasky
Feb 15, 2011·Journal of Pharmaceutical and Biomedical Analysis·B LiE Adams
Dec 25, 2012·Journal of Pharmaceutical and Biomedical Analysis·Yao-zuo YuanErwin Adams
Jan 24, 2013·Bioorganic & Medicinal Chemistry Letters·Lei ShaoWen Liu
Mar 23, 2013·Journal of Pharmaceutical and Biomedical Analysis·Yao-zuo YuanErwin Adams
Apr 22, 2014·Chemistry & Biology·Junhong GuoYuhui Sun
Jun 18, 2015·Chembiochem : a European Journal of Chemical Biology·Yawen GuHuanzhang Xia
Jan 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sicong LiYuhui Sun
Jan 16, 2019·Nature Chemical Biology·Yeon Hee BanYeo Joon Yoon

❮ Previous
Next ❯

Citations

Mar 12, 2021·Natural Product Reports·Zhengyan GuoYihua Chen

❮ Previous
Next ❯

Datasets Mentioned

BETA
JQ975418.1

Methods Mentioned

BETA
-phosphotransferases
PCR
nuclear magnetic resonance
deamination
Assay
1

Software Mentioned

GenB4
GenL

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Related Papers

The Journal of Antimicrobial Chemotherapy
L VerbistH Vanderhaeghe
Antimicrobial Agents and Chemotherapy
M J WeinsteinJ A Waitz
Chembiochem : a European Journal of Chemical Biology
Yawen GuHuanzhang Xia
© 2021 Meta ULC. All rights reserved