Unraveling the Role of Cytochrome P450 as a Key Regulator Lantipeptide Production in Streptomyces globisporus

Abstract

The aim of this study was to investigate the regulation of lantipeptide production in <i>Streptomyces globisporus</i> SP6C4, which produces the novel antifungal lantipeptides conprimycin and grisin, and to identify the role of cytochrome P450 (P450) in tis regulation. To investigate the regulation of lantipeptide production, we created gene deletion mutants, including Δ<i>P450</i>, Δ<i>tsrD</i>, Δ<i>lanM</i>, Δ<i>P450</i>Δ<i>tsrD</i>, and Δ<i>P450</i>Δ<i>lanM</i>. These mutants were characterized in terms of their morphology, sporulation, attachment, and antifungal activity against <i>Fusarium oxysporum</i>. The gene deletion mutants showed distinct characteristics compared to the wild-type strain. Among them, the Δ<i>P450</i>Δ<i>lanM</i> double mutant exhibited a recovery of antifungal activity against <i>F. oxysporum</i>, indicating that P450 plays a significant role in regulating lantipeptide production in <i>S. globisporus</i> SP6C4. Our findings highlight the significant role of P450 in the regulation of lantipeptide production and morphological processes in <i>S. globisporus</i>. The results suggest a potential link between P450-mediated metabolic pathways and the regulation of growth and secondary metabolism in SP6C4, thereby highlighting P450 as a putative target for the development of new antifungal agents.