Article ; Online: Production of (2S)-sakuranetin from (2S)-naringenin in Escherichia coli by strengthening methylation process and cell resistance
Synthetic and Systems Biotechnology, Vol 7, Iss 4, Pp 1117-
2022 Volume 1125
Abstract: 2S)-Sakuranetin is a 7-O-methylflavonoid that has anticancer, antiviral, and antimicrobial activities. Methylation process is involved in biosynthesizing (2S)-sakuranetin from (2S)-naringenin, in which S-adenosylmethionine (SAM) serves as the methyl ... ...
Abstract | (2S)-Sakuranetin is a 7-O-methylflavonoid that has anticancer, antiviral, and antimicrobial activities. Methylation process is involved in biosynthesizing (2S)-sakuranetin from (2S)-naringenin, in which S-adenosylmethionine (SAM) serves as the methyl donor. In this study, after methyl donor and substrate inhibition were identified as limiting factors for (2S)-sakuranetin biosynthesis, an efficient (2S)-sakuranetin-producing strain was constructed by enhancing methyl donor supply and cell tolerance to (2S)-naringenin. Firstly, PfOMT3 from Perilla frutescens was selected as the optimal flavonoid 7-O-methyltransferase (F7-OMT) for the conversion of (2S)-naringenin to (2S)-sakuranetin. Then, the methylation process was upregulated by regulating pyridoxal 5′-phosphate (PLP) content, key enzymes in methionine synthesis pathway, and the availability of ATP. Furthermore, genes that can enhance cell resistance to (2S)-naringenin were identified from molecular chaperones and sRNAs. Finally, by optimizing the fermentation process, 681.44 mg/L of (2S)-sakuranetin was obtained in 250-mL shake flasks. The titer of (2S)-sakuranetin reached 2642.38 mg/L in a 5-L bioreactor, which is the highest titer ever reported. This work demonstrates the importance of cofactor PLP in methylation process, and provides insights to biosynthesize other O-methylated flavonoids efficiently in E. coli. |
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Keywords | (2S)-Sakuranetin ; Flavonoid 7-O-methyltransferases ; Methylation ; Cell tolerance ; Metabolic engineering ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5 |
Subject code | 570 |
Language | English |
Publishing date | 2022-12-01T00:00:00Z |
Publisher | KeAi Communications Co., Ltd. |
Document type | Article ; Online |
Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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