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An Allele of Glutamate Formiminotransferase Triggers 5-Methyl-Tetrahydrofolate-to-MeFox Conversion and Facilitates Folate Biofortification in Maize

文献类型： 外文期刊

作者： Lian, Tong 1 ; Guo, Wenzhu 5 ; Wang, Yanjing 5 ; Wen, Weiwei 5 ; Wang, Weixuan 1 ; Jiang, Ling 1 ; Liang, Qiuju 1 ; Liu, Ji'an 1 ; Liu, Haijun 5 ; Xue, Yuan 5 ; Pan, Lixu 6 ; Liu, Qiaoquan 6 ; Yin, Ping 5 ; Zhang, Delin 5 ; Yan, Jianbing 5 ; Zhang, Chunyi 1 ;

作者机构： 1.Chinese Acad Agr Sci, Biotechnol Res Inst, Beijing 100081, Peoples R China

2.Hainan Acad Agr Sci, Sanya Inst, Sanya 572000, Peoples R China

3.Chinese Acad Agr Sci, Natl Nanfan Res Inst, Sanya 572000, Peoples R China

4.Hainan Acad Agr Sci, Inst Food Crops, Hainan Key Lab Crop Genet & Breeding, Haikou 571100, Peoples R China

5.Huazhong Agr Univ, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Peoples R China

6.Yangzhou Univ, Coll Agr, Key Lab Crop Genom & Mol Breeding Jiangsu Prov, Yangzhou 225009, Peoples R China

关键词： 5-methyl-tetrahydrofolate; folate metabolism; GFT; maize; MeFox

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

ISSN：

年卷期： 2025 年

页码：

收录情况： SCI

摘要： Identifying genes involved in folate accumulation is critical for elucidating the regulatory mechanisms of folate metabolism and breeding folate-rich crops. Here, a natural A-to-G variation at the 682nd bp is identified in the coding sequence of an identified plant gene glutamate formiminotransferase (GFT) in maize, leading to a glycine-to-asparagine substitution at the 228th in the protein sequence and contributing to the variation of folate accumulation in mature seeds of a maize inbred line population. This gene encodes a protein highly similar to the formiminotransferase domain of mammalian formiminotransferase cyclodeaminase. In vitro biochemical analysis of this protein reveals an activity of triggering 5-methyl-tetrahydrofolate (5-M-THF)-to-MeFox conversion, other than exerting an activity of formiminotransferase in mammals. Loss of ZmGFT function triples 5-M-THF levels, and overexpression of G-allele-carrying ZmGFT boosts the metabolic flow toward MeFox. Functional conservation of GFT is validated in rice and Arabidopsis. The asparagine-to-glycine substitution enhances 5-M-THF-to-MeFox conversion, as demonstrated by in vitro assays and in silico analyses. The functional characterization of the GFT gene has uncovered a new metabolic fate of 5-M-THF, apart from a C1 donor for methionine synthesis, in plants, and a distinct activity from its mammalian ortholog. The natural variation identified is useful for breeding folate-fortified maize varieties.

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