Bt Research 2025, Vol.16, No.3, 110-117 http://microbescipublisher.com/index.php/bt 114 5.3 Global regulators (Spo0A, AbrB, CodY). Some global regulatory factors play a core role in Bt, such as Spo0A, AbrB and CodY. They are closely related to cell differentiation, spore formation, metabolic regulation and stress response. Spo0A controls spore formation and toxin gene expression through the phosphorylation pathway, while the Rap-Phr system can influence Spo0A by dephosphorylating Spo0F, thereby changing population behavior and survival strategies (Gastelum et al., 2019). CodY can sense the amino acids and energy status within cells, regulate the expression of nutrition-related genes, and maintain a balance between growth and stress response (Peng et al., 2015). 5.4 Cross-talk between stress response and toxin gene regulation. There is a strong connection between the stress response of Bt and the regulation of toxin genes. Under alkaline conditions, the CRP/FNR family regulatory factor LtmR can directly regulate lactic acid metabolism, which affects the adaptability and virulence of Bt in the insect intestine. Under salt stress, antibiotic or pesticide stress, energy metabolism, stress protein and spore formation related pathways will be activated, and these changes will also affect the synthesis and secretion of toxin proteins (Guo et al., 2020; Subramanian et al., 2021). Furthermore, the MAPK signaling pathway can regulate the expression of Cry toxin receptor in host insects, thereby affecting the effect of Bt toxin. 6 Case Study: Transcriptomic Response of Bt to Oxidative Stress During Fermentation 6.1 Background: industrial fermentation exposes Bt to oxygen limitation followed by oxidative bursts. In industrial fermentation, Bacillus thuringiensis (Bt) often encounters the situation of insufficient oxygen. Later, due to increased ventilation or stirring, an oxidation explosion will suddenly occur again. Such an environment will cause a large amount of reactive oxygen species (ROS) to accumulate in cells, which will have an impact on metabolism, product synthesis and physiological balance. Therefore, understanding how Bt responds to this oxidative stress is of great significance for improving fermentation processes and enhancing strain stability. 6.2 Experimental setup (summarized from existing studies) Some studies used Bt 97-27 as a model to conduct knockout, complementarity and overexpression strains of hemH1 and hemH2 genes. Under different conditions of iron ions and H2O2 (simulated oxidative pressure), they observed the growth, tolerance and transcriptome changes of the strains. The study also used methods such as qRT-PCR and β -galactosidase activity detection to analyze the expression changes of genes related to heme synthesis, antioxidant stress and iron transport, and identified the regulatory relationships (Wang et al., 2025). 6.3 Key findings There are two types of iron chelases (HemH1 and HemH2) in Bt, which act differently under oxidative pressure. The ΔhemH2 mutant strain is particularly sensitive to H2O2. Supplementation of hemH1 or hemH2 can partially restore tolerance, while strains overexpressing hemH2 perform the best and have the strongest antioxidant capacity. The research also found that the iron uptake regulatory protein Fur can bind to and regulate the promoters of hemH1 and hemH2. The concentration of iron ions will affect the regulation mode, and the regulation direction will also reverse under oxidative pressure. When Bt is subjected to an oxidative burst, genes related to heme synthesis, the antioxidant system and ferrous transport are all upregulated. This indicates that Bt works together to combat oxidative stress by enhancing heme synthesis and antioxidant defense (Wang et al., 2025). 6.4 Implications These results indicate that Bt utilizes the Fur-hemH1/hemH2 regulatory axis during fermentation to flexibly regulate heme synthesis and the antioxidant system, thereby adapting to oxidative stress. This can not only maintain cellular homeostasis, but also provide molecular-level ideas for improving strain tolerance and optimizing processes in industrial fermentation.
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