Beyond Clavulanic Acid biosynthesis: Exploring the broad regulatory impact of BldD in Streptomyces clavuligerus ATCC 27064

by Luisa F. Patiño, Carlos Caicedo-Montoya, Rigoberto Ríos-Estepa BldD is a global regulator of morphological development in Streptomyces , usually acting as a repressor of aerial mycelium formation.

However, its role in metabolism and secondary biosynthesis in the wild-type strain Streptomyces clavuligerus remains poorly understood. In this study, we constructed a S.

clavuligerus strain overexpressing bldD and compared it with the empty vector control strain during fermentation in soy protein isolate medium. For this, transcriptomic analyses were performed at 24 h and 72 h.

We observed that BldD overexpression reduced CA production and repressed genes involved in cephamycin C biosynthesis, including lat and the pathway regulator ccaR . In contrast, genes associated with terpene biosynthesis, phage tail-like particles (CIS), and aerial mycelium formation ( bldN, bldM, chaplins ) were upregulated.

These changes suggest that BldD may directly and indirectly redirects metabolic flux away from β-lactam biosynthesis while promoting morphological differentiation, alternative defense systems and a potential link with GlcNAc metabolism.