Dynamic metabolic modeling of Streptomyces clavuligerus in complex medium highlights nutrient-dependent metabolic transitions associated with clavulanic acid biosynthesis.

ABSTRACT:

Background

Streptomyces clavuligerus is the main industrial producer of clavulanic acid (CA), a potent β-lactamase inhibitor. However, the metabolic interplay linking amino acid utilization, nitrogen regulation, and CA biosynthesis remains poorly understood, particularly under complex medium conditions.

Methods

The genome-scale metabolic model iLT1021 was used to simulate the dynamic metabolism of S. clavuligerus cultivated in GLYCAS-5 medium. Dynamic flux balance analysis (dFBA) captured the transition from primary to secondary metabolism, while robustness analysis and amino acid network topology identified key metabolic control nodes.

Results

Integration of dFBA with experimental exometabolome data revealed a clear temporal pattern of amino acid consumption: glutama

SUBMITTER: Toro-Navarro LF 

PROVIDER: S-EPMC12863558 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature