This study evaluates the effects of pyruvate decarboxylase and its lysine succinylation (Ksucc) on the development of Aspergillus flavus and the production of secondary metabolites. Mutant strains, including the knockout (∆pdc1), pdc1 point mutants (K258R and K258E) and complementary (∆pdc1.com) were constructed. The results showed that both Δpdc1 and K258R strains exhibited decreased conidiophore and conidia production and failed to generate sclerotia. The production of aflatoxin B1 (AFB1) was significantly increased in the Δpdc1 and K258R strains, while it decreased in the K258E strain. The results also indicate that pdc1 and its Ksucc are involved in the stress response and pathogenicity of A. flavus. Through GC-MS analysis, Δpdc1 was found to produce several significantly decreased compounds, including n-hexadecanoic acid, 2-bromotetradecane, and palmitic acid, among others. Additionally, different volatile metabolites, such as 1-iodo-decane, n, n-dimethyloctanamide and n, n-dimethyl-7-octynamide, were not detected in the Δpdc1 strain compared to WT and Δpdc1.com. HPLC results showed that the production of pyruvic acid, malic acid and succinic acid increased in both the Δpdc1 and K258R strains when compared to WT and Δpdc1.com strains. Comparative RNA-seq analysis revealed a total of 3,817 differentially expressed genes (DEGs) including 1,913 up-regulated and 1,904 down-regulated genes in Δpdc1 vs. WT. These results suggest that PDC1 and K258 play a crucial role in the biosynthesis of secondary metabolites, development and stress responses of A. flavus.

Microgravity (MG) and space radiation are two major environmental factors of space environment. Ionizing radiation generates reactive oxygen species (ROS) which plays a key role in radiation-induced DNA damage. Interestingly, simulated microgravity (SMG) also increases ROS production in various cell types. Thus, it is important to detect whether SMG could potentiate ROS production induced by genotoxins including radiation, especially at a minimal level not sufficient to induce detectable ROS. In this study, we treated mouse embryonic stem (MES) cells with H₂O₂ and SMG for 24 h. The concentration of H₂O₂ used was within 30 μmol/L at which intracellular ROS was the same as that in untreated cells. Exposure of cells to SMG for 24 h did not induce significantly higher levels of intracellular ROS than that of control cells either. Simultaneous exposure of cells to both SMG- and H₂O₂-induced ROS and apoptosis in MES cells. Although incubation in medium containing 5 or 30 μmol/L H₂O₂ induced a small enhancement of DNA double-strand breaks (DSBs), the addition of SMG treatment dramatically increased DSB levels. Taken together, SMG can significantly potentiate the effects of H₂O₂ at a low concentration that induce a small or negligible change in cells on ROS, apoptosis, and DNA damage. The results were discussed in relation to the combined effects of space radiation and MG on human body in this study.