D-对羟基苯甘氨酸生物合成研究进展

Proceedings of D-4-hydroxyphenylglycine Biosynthesis

D-对羟基苯甘氨酸是β-内酰胺类半合成抗生素药物中间体,广泛应用在医药领域。传统的D-对羟基苯甘氨酸的合成主要是化学合成和生物酶催化法。研究人员在天蓝色链霉菌中发现羟基扁桃氧化酶基因(hmo)、羟基扁桃酸合酶基因(hmas)和对羟基苯甘氨酸转移酶基因(hpgt)的基因簇。人们将来自不同菌种的hmo,hmas,hpgt基因整合到大肠杆菌中,实现了D-对羟基苯甘氨酸的生物全合成。

D-4-hydroxyphenylglycine is an important medicine intermediate of β-lactam semi-synthetic antibiotics such as penicillin and cephalosporin,and is widely used in the disease treatment.The traditional methods of D-4-hydroxyphenylglycine synthesis are chemical synthesis and enzyme catalysis.Previous researches proved that there is a gene cluster that contains hydroxymandelate synthase（hmas）,hydroxymandelate oxidase（hmo）,and the hydroxyphenylglycine aminotransferase（hpgt） in Streptomyces coelicolor.To produce D-HPG,these three genes were combined together in E.coli strains,which resulted in the first completely fermentative production of D-HPG.