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Biosynthesis of UDP-α-N-Acetyl-d-mannosaminuronic Acid and CMP-β-N-Acetyl-d-neuraminic Acid for the Capsular Polysaccharides of Campylobacter jejuni
Biochemistry ( IF 2.9 ) Pub Date : 2024-02-21 , DOI: 10.1021/acs.biochem.3c00664
Manas K. Ghosh 1 , Frank M. Raushel 1
Affiliation  

Campylobacter jejuni is a human pathogen and a leading cause of food poisoning in North America and Europe. The exterior surface of the bacterial cell wall is attached to a polymeric coat of sugar molecules known as the capsular polysaccharide (CPS) that helps protect the organism from the host immune response. The CPS is composed of a repeating sequence of common and unusual sugar residues. In the HS:11 serotype of C. jejuni, we identified two enzymes in the gene cluster for CPS formation that are utilized for the biosynthesis of UDP-α-N-acetyl-d-mannosaminuronic acid (UDP-ManNAcA). In the first step, UDP-α-N-acetyl-d-glucosamine (UDP-GlcNAc) is epimerized at C2 to form UDP-α-N-acetyl-d-mannosamine (UDP-ManNAc). This product is then oxidized by a NAD+-dependent C6-dehydrogenase to form UDP-ManNAcA. In the HS:6 serotype (C. jejuni strain 81116), we identified three enzymes that are required for the biosynthesis of CMP-β-N-acetyl-d-neuraminic acid (CMP-Neu5Ac). In the first step, UDP-GlcNAc is epimerized at C2 and subsequently hydrolyzed to form N-acetyl-d-mannosamine (ManNAc) with the release of UDP. This product is then condensed with PEP by N-acetyl-d-neuraminate synthase to form N-acetyl-d-neuraminic acid (Neu5Ac). In the final step, CMP-N-acetyl-d-neuraminic acid synthase utilizes CTP to convert this product into CMP-Neu5Ac. A bioinformatic analysis of these five enzymes from C. jejuni serotypes HS:11 and HS:6 identified other bacterial species that can produce UDP-ManNAcA or CMP-Neu5Ac for CPS formation.

中文翻译:

空肠弯曲杆菌荚膜多糖的 UDP-α-N-乙酰-d-甘露糖胺糖醛酸和 CMP-β-N-乙酰-d-神经氨酸的生物合成

空肠弯曲菌是一种人类病原体,也是北美和欧洲食物中毒的主要原因。细菌细胞壁的外表面附着一层糖分子的聚合物外壳,称为荚膜多糖(CPS),有助于保护生物体免受宿主免疫反应的影响。CPS 由常见和不寻常的糖残基的重复序列组成。在空肠弯曲菌的 HS:11 血清型中,我们在 CPS 形成基因簇中鉴定了两种酶,它们用于 UDP-α- N-乙酰基-d-甘露糖氨基糖醛酸 (UDP-ManNAcA) 的生物合成。第一步,UDP-α- N-乙酰基-d-葡萄糖胺 (UDP-GlcNAc) 在 C2 处差向异构化,形成 UDP-α- N-乙酰-d-甘露糖胺 (UDP-ManNAc)。然后该产物被 NAD +依赖性 C6-脱氢酶氧化形成 UDP-ManNAcA。在 HS:6 血清型(空肠弯曲菌菌株 81116)中,我们鉴定了 CMP-β- N-乙酰-d-神经氨酸(CMP-Neu5Ac)生物合成所需的三种酶。第一步,UDP-GlcNAc 在 C2 处差向异构化,随后水解形成N-乙酰-d-甘露糖胺 (ManNAc),并释放 UDP。然后该产物通过N-乙酰基-d-神经氨酸合酶与 PEP 缩合,形成N-乙酰基-d-神经氨酸 (Neu5Ac)。在最后一步中,CMP- N-乙酰基-d-神经氨酸合酶利用 CTP 将该产物转化为 CMP-Neu5Ac。对来自空肠弯曲菌血清型 HS:11 和 HS:6的这五种酶进行的生物信息学分析确定了可以产生用于 CPS 形成的 UDP-ManNAcA 或 CMP-Neu5Ac 的其他细菌物种。
更新日期:2024-02-21
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