Two Regulators of G-protein signaling (RGS) proteins FlbA1 and FlbA2 differentially regulate fumonisin B1 biosynthesis in Fusarium verticillioides

Fumonisins are a group of mycotoxins produced by maize pathogen Fusarium verticillioides that pose health concerns to humans and animals. Yet we still lack a clear understanding of the mechanism of fumonisins regulation during pathogenesis. The heterotrimeric G protein complex, which consists of G, G{beta}, and G{gamma} subunits, plays an important role in transducing signals under environmental stress. Furthermore, regulators of G-protein signaling (RGS) proteins act as negative regulators in heterotrimeric G protein signaling. Earlier studies demonstrated that G and G{beta} subunits are positive regulators of fumonisin B1 (FB1) biosynthesis and that two RGS genes, FvFlbA1 and FvFlbA2, were highly upregulated in G{beta} deletion mutant {Delta}Fvgbb1. Saccharomyces cerevisiae and Aspergillus nidulans contain a single copy of FlbA, but F. verticillioides has two putative FvFlbA paralogs, FvFlbA1 and FvFlbA2. Importantly, FvFlbA2 has a negative role in FB1 regulation. In this study, we further characterized functional roles of FvFlbA1 and FvFlbA2. While {Delta}FvflbA1 deletion mutant exhibited no significant defects, {Delta}FvflbA2 and {Delta}FvflbA2/A1 mutants showed thinner aerial hyphal growth while promoting FB1 production. FvFlbA2 is required for proper expression of key conidia regulation genes, including putative FvBRLA, FvWETA, and FvABAA, while suppressing FUM21, FUM1, and FUM8 expression. Split luciferase assays suggest that FvFlbA paralogs interact with key heterotrimeric G protein components to impact F. verticillioides FB1 production and asexual development.