D-phenylglycine (D-Phg) is an important side chain building block for semi-synthetic penicillins and cephalosporins such as ampicillin and cephalexin. To produce d-Phg ultimately from glucose, metabolic engineering was applied. Starting from phenylpyruvate, which is the direct precursor of L-phenylalanine, an artificial D-Phg biosynthesis pathway was created. This three-step route is composed of the enzymes hydroxymandelate synthase (HmaS), hydroxymandelate oxidase (Hmo), and the stereoinverting hydroxyphenylglycine aminotransferase (HpgAT). Together they catalyse the conversion of phenylpyruvate via mandelate and phenylglyoxylate to D-Phg. The corresponding genes were obtained from Amycolatopsis orientalis, Streptomyces coelicolor, and Pseudomonas putida. Combined expression of these activities in E. coli strains optimized for the production of L-phenylalanine resulted in the first completely fermentative production of D-Phg.

中文翻译：

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大肠杆菌L-苯丙氨酸途径的代谢工程，用于生产D-苯甘氨酸（D-Phg）。

D-苯基甘氨酸（D-Phg）是半合成青霉素和头孢菌素（如氨苄青霉素和头孢氨苄）的重要侧链结构单元。为了最终从葡萄糖中产生d-Phg，应用了代谢工程。从苯丙酮酸（L-苯丙氨酸的直接前体）开始，创建了人工D-Phg生物合成途径。此三步路线由羟扁桃酸合酶（HmaS），羟扁桃酸氧化酶（Hmo）和立体转化羟苯基甘氨酸氨基转移酶（HpgAT）组成。它们共同催化了扁桃酸酯和苯乙醛酸苯丙酮酸酯转化为D-Phg。相应的基因获自东方的支链淀粉菌，天生链霉菌和恶臭假单胞菌。这些活动在大肠杆菌中的联合表达。