Forming folate-fortified rice | Nature Chemical Biology

Folates are a group of water-soluble B vitamins that are essential for all organisms. Although plants and microbes can synthesize them, humans cannot, and insufficient intake of folates can

lead to several disorders. It is therefore important to find folate sources that can help alleviate folate malnutrition. Cereals are poor sources of folates but contain high levels of MeFox,

a pyrazino-s-triazine derivative of 4α-hydroxy-5-methyltetrahydrofolate that is a biologically inactive, oxidized form of folate, suggesting potential for targeting its formation. Now,

Liang et al. have enhanced the metabolic flux by co-overexpression of two folate biosynthesis genes and blocked folate oxidation via gene editing to create folate-biofortified rice.

The team identified and validated OsGFT as having a crucial role in MeFox formation in rice. Its targeted knockout by CRISPR–Cas9 editing resulted in rice plants with elevated levels of

5-methyltetrahydrofolate as well as other biologically active folates. Next, the team combined their gene editing strategy with the overexpression of Arabidopsis genes GTP cyclohydrolase 1

(GCH1) and aminodeoxychorismate synthase (ADCS), responsible for the first steps in the biosynthesis of key components of the folate scaffold. This led to transgenic plants containing total

folate levels up to 13-fold higher than the wild type (WT), and the MeFox average content was 33% of that of the WT. Furthermore, no plant nor seed showed phenotypic differences from the WT,

and the team demonstrated that the increased levels of folates were also found in milled rice. This study showcased the potential for engineered whole grain rice to address deficiencies in

folate nutrition.

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