3,4-二羟基扁桃酸在大肠杆菌中的生物合成

Biosynthesis of 3,4-dihydroxymandelic Acid in an Engineered Escherichia coli Strain

3,4-二羟基扁桃酸是许多药物和香料合成的重要中间体,具有较强的抗氧化和清除自由基的活性。旨在实现3,4-二羟基扁桃酸在大肠杆菌中的从头合成。通过在大肠杆菌MG1655/ΔA中过表达来源于天蓝色链霉菌(Streptomyces coelicolor)的对羟基扁桃酸合酶(HmaS)和大肠杆菌的羟化酶(HpaBC)基因,实现了以葡萄糖为原料生物合成3,4-二羟基扁桃酸;并经IPTG和蛋白诱导温度初步优化后,摇瓶发酵36 h 3,4-二羟基扁桃酸的产量达到240 mg/L。

3,4-dihydroxymandelic acid,an important pharmaceutical and spices intermediate,possesses strong antioxidativeand radical scavenging activities. To achieve the de novo biosynthesis of 3,4-dihydroxymandelic acid in Escherichia coli,the genes ofhydroxymandelate synthase（HmaS）from Streptomyces coelicolor and 4-hydroxyphenylacetate 3-hydroxylase（HpaBC）from E. coli werecloned into pTrc His B and overexpressed in an engineered E. coli strain MG1655/ΔA. After induction of IPTG and optimization of the inducingtemperature,the yield of 3,4-dihydroxymandelic acid reached 240 mg/L in shake flask after 36 hours fermentation,laying a foundation for thelarge-scale fermentation production of 3,4-dihydroxymandelic acid.