Zheng Xianyao, Wu Shuaishuai, Qiu Jiangbing, Li Aifeng, Li Ling, Yan Guowang, Li Min, Meng Fanping, Zhang Kaidian, Lin Senjie
Department of Environmental Science, College of Environmental Science and Engineering, Ocean University of China, Qingdao 266100, China.
Ministry of Education Key Laboratory of Marine Environment and Ecology, Ocean University of China, Qingdao 266100, China.
Proc Natl Acad Sci U S A. 2025 Jun 17;122(24):e2424843122. doi: 10.1073/pnas.2424843122. Epub 2025 Jun 9.
The β--methylamino--alanine (BMAA) is an emerging neurotoxin associated with human neurodegenerative diseases such as Alzheimer's disease. Here, we report the prevalence of BMAA synthesis in protein forms by marine diatoms and reconstruct its tentative biosynthesis pathway. Remarkably, the BMAA production is strongly induced by iron limitation. Transcriptomic analyses suggest that cysteine synthase (CysK) is involved in BMAA synthesis. This is verified as CRISPR/Cas9-based CysK knockout abolished BMAA production and addition of the recombinant CysK to the mutant restored BMAA synthesis. As diatoms are the most abundant primary producers in ocean, the prevalence of BMAA in diatoms has significant public health implications. The biosynthesis pathway provides biomarkers for further investigation of BMAA production in marine diatoms and insights for understanding the pathological mechanism for human neurodegenerative diseases.
β-甲基氨基丙氨酸（BMAA）是一种新出现的神经毒素，与阿尔茨海默病等人类神经退行性疾病有关。在此，我们报告了海洋硅藻以蛋白质形式合成BMAA的普遍性，并重建了其初步的生物合成途径。值得注意的是，铁限制强烈诱导BMAA的产生。转录组分析表明，半胱氨酸合酶（CysK）参与BMAA的合成。基于CRISPR/Cas9的CysK基因敲除消除了BMAA的产生，而向突变体中添加重组CysK恢复了BMAA的合成，这证实了上述结论。由于硅藻是海洋中最丰富的初级生产者，硅藻中BMAA的普遍性具有重大的公共卫生意义。该生物合成途径为进一步研究海洋硅藻中BMAA的产生提供了生物标志物，并为理解人类神经退行性疾病的病理机制提供了见解。
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