L-2,3-Diaminopropionate Binding Mode of the SulM Adenylation Domain Limits Engineering Monobactam Analogue Biosynthesis with Larger Substrates.

ABSTRACT: The simple but essential azetidinone core of the β-lactam antibiotics is uniquely N-sulfonated in the monobactam subfamily. This feature confers both target binding specificity to inactivate bacterial cell wall biosynthesis (antibiosis) and structural differentiation to elude destruction by metallo-β-lactamases (MBLs). The recent FDA approval of Emblaveo to treat serious bacterial infections combines an established synthetic monobactam aztreonam and avibactam, which additionally blocks serine β-lactamases, to create a broadly effective antibacterial therapeutic. Here we report experiments to capture the native monobactam biosynthetic steps to the natural product sulfazecin with the aim of accessing new monobactams by reprogramming its biosynthetic machinery. In sulfazecin biosynthesis, the

SUBMITTER: Kahlert L 

PROVIDER: S-EPMC12042044 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature