Improving activity of GenB3 and GenB4 in gentamicin dideoxygenation biosynthesis by semi-rational engineering.

ABSTRACT:

Background

Aminoglycoside antibiotics continue to play an indispensable role in clinical antibacterial agents. However, the protection and deprotection procedures in the chemical pathways of semi-synthetic antibiotics are long, atom- and step-inefficient, which severely hampers the development of novel AGs.

Results

Here, GenB3 and GenB4 are employed to synthesize sisomicin, Oxo-verdamicin, Oxo-gentamicin C1a, and Oxo-gentamicin C2a. Subsequently, a semi-rational strategy is applied to enhance the activities of GenB3 and GenB4. The activity of GenB3^M1 (Q270N) towards JI-20A-P is 1.74 times higher than that of GenB3^WT. Similarly, the activity of GenB3^M2 (L361C/A412T/Q270N) towards JI-20Ba-P is 1.34 times higher than that of GenB3^WT.

SUBMITTER: Zhai H 

PROVIDER: S-EPMC11869428 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature