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 canonical subunits and various regulators of G-protein signaling (RGS) proteins, plays an important role in transducing signals under environmental stress. Earlier studies demonstrated that Gα and Gβ subunits are positive regulators of fumonisin B1 (FB1) biosynthesis and that two RGS genes, FvFlbA1 and FvFlbA2, were highly upregulated in Gβ deletion mutant ∆Fvgbb1. Notably, FvFlbA2 has a negative role in FB1 regulation. While many fungi contain a single copy of FlbA, F. verticillioides harbors two putative FvFlbA paralogs, FvFlbA1 and FvFlbA2. In this study, we further characterized functional roles of FvFlbA1 and FvFlbA2. While ∆FvflbA1 deletion mutant exhibited no significant defects, ∆FvflbA2 and ∆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 determined that FvFlbA paralogs interact with key heterotrimeric G protein components, which in turn will lead altered G-protein-mediated signaling pathways that regulate FB1 production and asexual development in F. verticillioides.

伏马菌素是一组由玉米病原体轮枝镰刀菌产生的霉菌毒素，对人类和动物的健康构成威胁。然而，我们对伏马菌素在发病过程中的调控机制仍缺乏清晰的认识。异源三聚体 G 蛋白复合物由规范亚基和 G 蛋白信号转导 (RGS) 蛋白的各种调节剂组成，在环境压力下的信号转导中起着重要作用。早期研究表明 Gα 和 Gβ 亚基是伏马菌素 B1 (FB1) 生物合成的正调节因子，并且两个 RGS 基因 FvFlbA1 和 FvFlbA2 在 Gβ 缺失突变体 ΔFvgbb1 中高度上调。值得注意的是，FvFlbA2 在 FB1 调节中具有负面作用。虽然许多真菌只含有一个 FlbA 拷贝，但轮枝杆菌包含两个假定的 FvFlbA 旁系同源物，FvFlbA1 和 FvFlbA2。在这项研究中，我们进一步表征了 FvFlbA1 和 FvFlbA2 的功能作用。虽然 ∆FvflbA1 缺失突变体没有表现出明显的缺陷，但 ∆FvflbA2 和 ∆FvflbA2/A1 突变体在促进 FB1 生产的同时显示出更薄的气生菌丝生长。FvFlbA2 是关键分生孢子调控基因（包括推定的FvBRLA、FvWETA和FvABAA）的正确表达所必需的，同时抑制FUM21、FUM1和FUM8表达。分裂荧光素酶测定确定 FvFlbA 旁系同源物与关键的异源三聚体 G 蛋白成分相互作用，这反过来将导致改变 G 蛋白介导的信号通路，从而调节轮枝杆菌中FB1 的产生和无性发育。