Key genes for arsenobetaine synthesis in marine medaka (Oryzias melastigma) by transcriptomics

Marine fish undergo detoxification to overcome As stress, forming non-toxic metabolites arsenobetaine (AsB). Genes associated with AsB synthesis remain unknown. Therefore, in this study, we explored the key genes involved in the synthesis of AsB by transcriptomic analysis in marine medaka (Oryzias melastigma), and then screened candidate genes related to AsB synthesis. In the liver, 40 genes were up-regulated and 23 genes were down-regulated, whereas in muscle, 83 genes were up-regulated and 331 genes were down-regulated. We revealed that bhmt, mat2aa, and gstt1a can play a significant role in the glutathione and methionine metabolic pathway. These three genes can affect the conversion of arsenocholine (AsC) to AsB by the vitro gene transformation experiments of E. coli BL21(DE3). E. coli BL21-bhmt overexpressing bhmt resulted in more oxidation of precursor AsC to AsB. Furthermore, the AsB concentration was decreased after E. coli BL21 overexpressing mat2aa and gstt1a, which were down-regulated in marine medaka. Therefore, we concluded that bhmt, mat2aa, and gstt1a are involved in AsB synthesis. Overall, this is the first report on transcriptome screening and identification of key genes for AsB synthesis in marine medaka. We provided important insights to reveal the mystery of AsB synthesis in marine fish.