Escherichia coli glutamate decarboxylase (EcGadB), a pyridoxal 5’-phosphate (PLP)-dependent enzyme, is highly specific for L-glutamate and was demonstrated to be effectively immobilised for the production of γ-aminobutyric acid (GABA), its decarboxylation product. Herein we show that EcGadB quantitatively decarboxylates the L-isomer of D,L-2-amino-4-(hydroxyphosphinyl)butyric acid (D,L-Glu-γ-P_H), a phosphinic analogue of glutamate containing C-P-H bonds. This yields 3-aminopropylphosphinic acid (GABA-P_H), a known GABA_B receptor agonist and provides previously unknown D-Glu-γ-P_H, allowing us to demonstrate that L-Glu-γ-P_H, but not D-Glu-γ-P_H, is responsible for D,L-Glu-γ-P_H antibacterial activity. Furthermore, using GABase, a preparation of GABA-transaminase and succinic semialdehyde dehydrogenase, we show that GABA-P_H is converted to 3-(hydroxyphosphinyl)propionic acid (Succinate-P_H). Hence, PLP-dependent and NADP⁺-dependent enzymes are herein shown to recognise and metabolise phosphinic compounds, leaving unaffected the P-H bond. We therefore suggest that the phosphinic group is a bioisostere of the carboxyl group and the metabolic transformations of phosphinic compounds may offer a ground for prodrug design.

大肠杆菌谷氨酸脱羧酶 ( Ec GadB) 是一种 5'-磷酸吡哆醛 (PLP) 依赖性酶，对L-谷氨酸具有高度特异性，并被证明可有效固定用于 γ-氨基丁酸 (GABA) 的生产，其脱羧作用产品。在这里，我们表明Ec GadB 定量脱羧D,L -2-amino-4-(hydroxyphosphinyl)butyric acid ( D,L -Glu-γ- PH) 的L-异构体， D,L -Glu-γ- _PH是一种含有CPH键的谷氨酸的次膦酸类似物。这会产生 3-氨基丙基次膦酸 (GABA-PH ₎，一种已知的 GABA _B受体激动剂，并提供以前未知的D -Glu-γ-P _H，使我们能够证明L -Glu-γ-P _H而非D -Glu-γ-P _H负责D,L -Glu-γ-P _H抗菌活性。此外，我们使用 GABase（一种 GABA-转氨酶和琥珀酸半醛脱氢酶的制剂）证明 GABA-P _H被转化为 3-(羟基次膦酰基)丙酸 (Succinate-P _H )。因此，本文显示 PLP 依赖性和 NADP ⁺依赖性酶可识别和代谢次膦酸化合物，不影响PH纽带。因此，我们认为次膦酸基团是羧基的生物电子等排物，次膦酸化合物的代谢转化可能为前药设计提供基础。