Functional insights into <i>Streptomyces</i> isolates containing both clavulanic acid-like and carbapenem biosynthetic gene clusters

The global rise of antimicrobial resistance calls for innovative strategies to preserve the efficacy of existing antibiotics and identify new therapeutic agents. This study explores naturally occurring β-lactamase inhibitors and antibiotics beyond well-characterized systems. Investigation of clavulanic acid (CA)-like and MM 4550-like biosynthetic gene clusters (BGCs) in <i>Streptomyces pratensis</i> and related environmental isolates revealed a broader occurrence of monocyclic β-lactam precursors and dual-function carbapenems in nature. These findings offer new insights into β-lactam co-production and further indicate that unlinked β-lactam BGCs may have functional significance. The study also highlights the importance of exploring silent counterparts of known BGCs as potential sources of bioactive metabolites, enhancing our understanding of β-lactam BGC diversity and evolution. Notably, it identifies β-lactamase inhibitor and antibiotic-producing strains, opening new avenues for discovering antibiotic-inhibitor combinations of relevance.