Bt Research 2025, Vol.16, No.5, 182-193 http://microbescipublisher.com/index.php/bt 182 Research Report Open Access Metabolic Pathways in Bt: Unveiling the Biochemical Basis of Insect Pathogenicity Jun Wang, Mengyue Chen Animal Science Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: mengyue.chen@cuixi.org Bt Research, 2025, Vol.16, No.5 doi: 10.5376/bt.2025.16.0021 Received: 03 Jul., 2025 Accepted: 20 Aug., 2025 Published: 05 Sep., 2025 Copyright © 2025 Wang and Chen, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang J., and Chen M.Y., 2025, Metabolic pathways in Bt: unveiling the biochemical basis of insect pathogenicity, Bt Research, 16(5): 182-193 (doi: 10.5376/bt.2025.16.0021) Abstract Bacillus thuringiensis, as an important microbial insecticide, has an irreplaceable position in agriculture and public health. Bt can produce spores and sporophor crystal toxins during metabolism, and has a highly specific pathogenic activity against a variety of insects and is safe for humans and animals. This study reviews the main metabolic pathways of Bt and their relationship with pathogenicity, including sugar metabolism energy supply, protein and amino acid metabolism regulation, lipid metabolism and cell membrane function, as well as the synthesis mechanism, energy demand and expression regulation of Bt toxins (Cry, Cyt, etc.). We also discussed the role of secondary metabolites produced by Bt (such as antimicrobial peptides, pigments, etc.) in insect lethality, as well as the mechanism of metabolic regulatory networks and signaling in Bt pathogenic processes. This study takes corn borer control as an example to analyze the survival adaptation mechanism and key metabolic links of Bt in the insect intestine, and explores the metabolic optimization strategy of genetically engineered Bt corn, and looks forward to the future prospects and challenges of Bt research in metabolomics, metabolic pathway transformation and green agriculture applications. Keywords Bacillus thuringiensis; Metabolic pathway; Insecticidal mechanism; Secondary metabolites; Insect intestine 1 Introduction Bacillus thuringiensis (Bt) is a Gram-positive Bacillus known for producing crystalline proteins (δ-endotoxins) with insecticidal activity. Because of its high virulence to target insects and relatively safe against non-target organisms and the environment, Bt preparations are considered one of the important alternatives to chemical pesticides. At the same time, the Bt toxin gene was also transferred into crops to cultivate genetically modified insect-resistant crops, which greatly reduced the amount of chemical pesticides (Rajadurai et al., 2023). With the long-term use of Bt preparations and Bt crops, pest resistance problems gradually emerged, and some field populations developed resistance to Bt toxins. According to statistics, as of 2020, more than 10 species of field pests have reported resistance to Bt. This situation has triggered the need for more in-depth research on the Bt insecticidal mechanism and the exploration of how to improve the virility and overcome resistance of Bt strains through metabolic pathway modification (Peralta et al., 2021). The pathogenic mechanism of Bt on insects has long attracted much attention. The currently widely accepted model is that after insects feed on preparations containing Bt spores and crystals, the alkaline intestinal environment dissolves the crystals and releases protoxins, and insect intestinal proteases activate it as toxins. The toxin binds to the midgut epithelial receptor and forms holes, resulting in intestinal cell rupture and insect death. Studies have suggested that the insecticide effect of Bt may not only be the crystal toxin itself: live bacteria proliferate in insects and their secondary metabolites produced may also be involved in the pathogenic process. For example, there is evidence that the existence of insect intestinal flora is closely related to the results of Bt infection. Some scholars have observed that sterile insects have reduced sensitivity to Bt (Xu et al., 2023), and it is speculated that Bt infection may require synergistic effects of insect intestinal flora to cause sepsis and other effects. These controversies suggest that we need to examine the pathogenic mechanism of Bt from a broader perspective, including the role of metabolic pathways in it. The metabolic pathway runs through the entire process of Bt from vegetative growth to sporogenic toxin formation, and has a fundamental impact on its pathogenic properties. This study will review the main metabolic
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