MUROPEPTIDE RECYCLING PATHWAY & BETA LACTAMASE INDUCTION

这项建议的主要目的是阐明所使用的途径 由大肠杆菌回收肌多肽，以确定功能回收 在细胞的生命中起作用，并表征肌多肽的作用 在β-内酰胺酶诱导过程中。这些目标源于我们的 初步结果支持以下暂定结论：(1) AmpG是一种渗透酶，是诱导β-内酰胺酶所必需的。 回收细胞壁组件所需的。(2)AMPG最有可能 转运N-乙酰氨基葡萄糖基-β1-4，1，6-脱水-N-乙酰胞壁酰胺-L- 丙氨酰-D-谷氨酰基-(L)-中位二氨基甲酸(G1cNAc-anhMurNac-L-ALA-D- Glu-DAP)进入细胞质。(3)β-内酰胺酶必需的AmpD 诱导性对于回收也是至关重要的。(4)ampD突变体积累 大量的AnhMurNAc-L-ALA-D-Glu-DAP表明它是一种诱导 莱兰德。(5)AmpD是一种anhMurNAc-1-Ala酰胺酶。据推测， AmpD酰胺酶释放的三肽以一种尚未完成的方式添加到UDPMurNAc中 发现三肽加成酶从而重新引入L-丙氨酸-D-谷氨酸- DAP进入生物合成途径。(6)G1cNAc-anhMurNac-L-丙氨酸-D-谷氨酸-DAP 可能是另一种β-内酰胺酶的诱导剂。因此，基于这些新的 结果过去16个月，具体目标是： 1.研究和表征回收中的4个预测步骤 途径，即：AMPG渗透酶、β-N-乙酰氨基葡萄糖苷酶、AmpD 酰胺酶，以及假想的三肽加成酶。 2.鉴定与β-内酰胺酶诱导有关的神经肽和 以进一步确定它们在诱导β-内酰胺酶中的作用。 3.寻找循环利用在细胞寿命中的作用。

The principal objectives of this proposal are to elucidate the pathway used by E. coli for recycling muropeptides, to determine the function recycling serves in the life of the cell and to characterize the role of muropeptides in the beta-lactamase induction process. These objectives follow from our preliminary results which support the following tentative conclusions: (1) AmpG, which is required for beta-lactamase induciton, is a permease required for recycling cell wall components. (2) AmpG most likely transports N-acetylglucosaminyl-beta 1-4, 1,6 anhydro-N-acetylmuramyl-L- alanyl-D-glutamyl-(L)-meso-diaminopimelic acid (G1cNAc-anhMurNAc-L-ala-D- glu-DAP) into the cytoplasm. (3) AmpD, required for beta-lactamase inducibility is also essential for recycling. (4) ampD mutants accumulate huge amounts of anhMurNAc-L-ala-D-glu-DAP indicating that it is an inducing ligand. (5) AmpD is an anhMurNAc-1-ala amidase. Presumably the tripeptide released by the AmpD amidase is added to UDPMurNAc by a yet to be discovered tripeptide-adding enzyme thereby reintroducing L-ala-D-glu- DAP into the biosynthetic pathway. (6) G1cNAc-anhMurNAC-L-ala-D-glu-DAP is probably another inducer of beta-lactamase. Thus, based on these new results of the past 16 months, the specific aims are: 1. To study and characterize the 4 predicted steps in the recycling pathway, namely: AmpG permease, beta-N-acetylglucosaminidase, AmpD amidase, and the hypothetical tripeptide-adding enzyme. 2. To identify the muropeptides involved in beta-lactamase induction and to further characterize their role in beta-lactamase induction. 3. To search for a role of recycling in the life of the cell.