The LuxR family regulator SAV111 enhances avermectin production by binding to aveA1 gene promoter in Streptomyces avermitilis

Avermectins, macrocyclic lactones produced by Streptomyces avermitilis, serve as essential therapeutic and agrochemical agents. LuxR-type transcriptional regulators are multifunctional proteins known to orchestrate antibiotic biosynthesis alongside virulence modulation, biofilm dynamics, and host immune interactions. However, no prior studies have characterized LuxR-family proteins as direct regulators of avermectin biosynthesis. This study delineates the mechanism through which SAV111, a LuxR-family transcriptional activator, enhances avermectin biosynthesis. Batch fermentation of the SAV111-overexpressing strain demonstrated dual functionality: (1) significant upregulation of avermectin titers and (2) accelerated hyphal growth kinetics. Developmental profiling revealed precocious morphological differentiation in the overexpression strain compared to wild-type controls. Electrophoretic mobility shift assays confirmed direct binding of SAV111 to the aveA1 promoter, encoding the synthase catalytic subunit within the pathway of avermectin biosynthetic. Transcriptional activation of aveA1 represents the primary mechanism underlying SAV111-mediated avermectin overproduction. These findings advance the understanding of LuxR-family regulatory networks in secondary metabolism and establish a molecular framework for engineering hyperproductive S. avermitilis strains.