Xie Rui, Zhuang Zhenhong, Chen Qionghui, Xie Chunlan, Adejor John, Nie Xinyi, Wang Shihua
State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Fujian Key Laboratory of Pathogenic Fungi and Mycotoxins, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
Virulence. 2025 Dec;16(1):2532812. doi: 10.1080/21505594.2025.2532812. Epub 2025 Jul 18.
and its secondary metabolites, aflatoxins (AFs), especially aflatoxin B1 (AFB1), seriously affect agricultural production, food storage, and human health. Succinyl-CoA synthase ADP-forming subunit β (SCS) is involved in the synthesis of succinate from succinyl-CoA in the tricarboxylic acid cycle. In this study, we demonstrated that SCS led to decreased aflatoxin production. Bioassay results showed that deletion of (the gene coding for SCS) led to increased succinyl-CoA accumulation. Catalyzed by succinyl transferase (STA), the increased amount of succinyl-CoA in Δ leads to increased levels of global protein succinylation, which causes upregulation of AFB1 accumulation in Δ. To elucidate the mechanism of increased AFB1 accumulation in Δ, the relevant enzymes and metabolites involved in the aflatoxin biosynthesis pathway were examined through proteome and metabolome analyses. These data illustrate that the deletion of results in an increase in (1'S, 5'S) - averufin catalyzed by AflK, (1'S)-averantin catalyzed by AflD, and aflatoxin G2/O- methylsterigmatocystin catalyzed by AflP. We also found that AflM is not only upregulated but also succinylated in Δ; Ach1 (acetyl-CoA hydrolase, Ach1) is downregulated in Δ and interacts with SCS. Therefore, we deduce a pathway of Ach1/STA-SCS-succinylated AflM for AFB1 biosynthesis, which provides knowledge for the control of and AFs.
及其次级代谢产物黄曲霉毒素（AFs），尤其是黄曲霉毒素B1（AFB1），严重影响农业生产、食品储存和人类健康。琥珀酰辅酶A合成酶ADP形成亚基β（SCS）参与三羧酸循环中由琥珀酰辅酶A合成琥珀酸的过程。在本研究中，我们证明SCS可导致黄曲霉毒素产量降低。生物测定结果表明，（编码SCS的基因）缺失导致琥珀酰辅酶A积累增加。在琥珀酰转移酶（STA）的催化下，Δ中增加的琥珀酰辅酶A量导致全局蛋白质琥珀酰化水平升高，这导致Δ中AFB1积累上调。为了阐明Δ中AFB1积累增加的机制，通过蛋白质组和代谢组分析检测了黄曲霉毒素生物合成途径中相关的酶和代谢产物。这些数据表明，的缺失导致由AflK催化的（1'S，5'S） - 疣孢青霉烯醇、由AflD催化的（1'S）-疣孢菌素和由AflP催化的黄曲霉毒素G2/O-甲基柄曲霉素增加。我们还发现AflM不仅在Δ中上调而且被琥珀酰化；Ach1（乙酰辅酶A水解酶，Ach1）在Δ中下调并与SCS相互作用。因此，我们推断出一条用于AFB1生物合成的Ach1/STA-SCS-琥珀酰化AflM途径，这为控制和AFs提供了知识。
