title: Efficient synthesis of eriodictyol from L-tyrosine in Escherichia coli.
abstract: The health benefits of flavonoids for humans are increasingly attracting attention. Because the extraction of high-purity flavonoids from plants presents a major obstacle, interest has emerged in biosynthesizing them using microbial hosts. Eriodictyol is a flavonoid with anti-inflammatory and antioxidant activities. Its efficient synthesis has been hampered by two factors: the poor expression of cytochrome P450 and the low intracellular malonyl coenzyme A (malonyl-CoA) concentration in Escherichia coli. To address these issues, a truncated plant P450 flavonoid, flavonoid 3'-hydroxylase (tF3'H), was functionally expressed as a fusion protein with a truncated P450 reductase (tCPR) in E. coli. This allowed the engineered E. coli to produce eriodictyol from l-tyrosine by simultaneously coexpressing the fusion protein with tyrosine ammonia lyase (TAL), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), and chalcone isomerase (CHI). In addition, metabolic engineering was employed to enhance the availability of malonyl-CoA so as to achieve a new metabolic balance and rebalance the relative expression of genes to enhance eriodictyol accumulation. This approach made the production of eriodictyol 203% higher than that in the control strain. By using these strategies, the production of eriodictyol from l-tyrosine reached 107 mg/liter. The present work offers an approach to the efficient synthesis of other hydroxylated flavonoids from l-tyrosine or even glucose in E. coli.
authors.affiliation: Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Saijie
authors.initials: S
authors.lastname: Zhu
authors.forename: Junjun
authors.initials: J
authors.lastname: Wu
authors.forename: Guocheng
authors.initials: G
authors.lastname: Du
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D044950:Flavanones / Q000096:biosynthesis*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D060847:Metabolic Engineering; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D044950:Flavanones; D014443:Tyrosine; D008316:Malonyl Coenzyme A; C007619:eriodictyol