Coderch Núria, Piqué Núria, Lindner Buko, Abitiu Nihal, Merino Susana, Izquierdo Luis, Jimenez Natalia, Tomás Juan M, Holst Otto, Regué Miguel
Departamento de Microbiología y Parasitología Sanitarias, Facultad de Farmacia, Universidada de Barcelona, 08028 Barcelona, Spain.
J Bacteriol. 2004 Feb;186(4):978-88. doi: 10.1128/JB.186.4.978-988.2004.
The gene cluster (waa) involved in Serratia marcescens N28b core lipopolysaccharide (LPS) biosynthesis was identified, cloned, and sequenced. Complementation analysis of known waa mutants from Escherichia coli K-12, Salmonella enterica, and Klebsiella pneumoniae led to the identification of five genes coding for products involved in the biosynthesis of a shared inner core structure: [L,D-HeppIIIalpha(1-->7)-L,D-HeppIIalpha(1-->3)-L,D-HeppIalpha(1-->5)-KdopI(4<--2)alphaKdopII] (L,D-Hepp, L-glycero-D-manno-heptopyranose; Kdo, 3-deoxy-D-manno-oct-2-ulosonic acid). Complementation and/or chemical analysis of several nonpolar mutants within the S. marcescens waa gene cluster suggested that in addition, three waa genes were shared by S. marcescens and K. pneumoniae, indicating that the core region of the LPS of S. marcescens and K. pneumoniae possesses additional common features. Chemical and structural analysis of the major oligosaccharide from the core region of LPS of an O-antigen-deficient mutant of S. marcescens N28b as well as complementation analysis led to the following proposed structure: beta-Glc-(1-->6)-alpha-Glc-(1-->4))-alpha-D-GlcN-(1-->4)-alpha-D-GalA-[(2<--1)-alpha-D,D-Hep-(2<--1)-alpha-Hep]-(1-->3)-alpha-L,D-Hep[(7<--1)-alpha-L,D-Hep]-(1-->3)-alpha-L,D-Hep-[(4<--1)-beta-D-Glc]-(1-->5)-Kdo. The D configuration of the beta-Glc, alpha-GclN, and alpha-GalA residues was deduced from genetic data and thus is tentative. Furthermore, other oligosaccharides were identified by ion cyclotron resonance-Fourier-transformed electrospray ionization mass spectrometry, which presumably contained in addition one residue of D-glycero-D-talo-oct-2-ulosonic acid (Ko) or of a hexuronic acid. Several ions were identified that differed from others by a mass of +80 Da, suggesting a nonstoichiometric substitution by a monophosphate residue. However, none of these molecular species could be isolated in substantial amounts and structurally analyzed. On the basis of the structure shown above and the analysis of nonpolar mutants, functions are suggested for the genes involved in core biosynthesis.
已鉴定、克隆并测序了粘质沙雷氏菌N28b核心脂多糖(LPS)生物合成中涉及的基因簇(waa)。对来自大肠杆菌K-12、肠炎沙门氏菌和肺炎克雷伯菌的已知waa突变体进行互补分析,鉴定出五个编码参与共享内核心结构生物合成产物的基因:[L,D-庚糖IIIα(1→7)-L,D-庚糖IIα(1→3)-L,D-庚糖Iα(1→5)-KdoI(4←2)αKdoII](L,D-庚糖,L-甘油-D-甘露庚吡喃糖;Kdo,3-脱氧-D-甘露辛-2-酮糖酸)。对粘质沙雷氏菌waa基因簇内几个非极性突变体的互补和/或化学分析表明,此外,粘质沙雷氏菌和肺炎克雷伯菌共有三个waa基因,这表明粘质沙雷氏菌和肺炎克雷伯菌LPS的核心区域具有其他共同特征。对粘质沙雷氏菌N28b的O抗原缺陷突变体LPS核心区域的主要寡糖进行化学和结构分析以及互补分析,得出以下推测结构:β-Glc-(1→6)-α-Glc-(1→4))-α-D-GlcN-(1→4)-α-D-GalA-[(2←1)-α-D,D-庚糖-(2←1)-α-庚糖]-(1→3)-α-L,D-庚糖[(7←1)-α-L,D-庚糖]-(1→3)-α-L,D-庚糖-[(4←1)-β-D-Glc]-(1→5)-Kdo。β-Glc、α-GclN和α-GalA残基的D构型是根据遗传数据推导出来的,因此是暂定的。此外,通过离子回旋共振-傅里叶变换电喷雾电离质谱法鉴定出其他寡糖,推测这些寡糖还含有一个D-甘油-D-塔罗辛-2-酮糖酸(Ko)或己糖醛酸残基。鉴定出几个离子,它们与其他离子的质量相差80 Da,表明存在单磷酸残基的非化学计量取代。然而,这些分子种类均无法大量分离并进行结构分析。根据上述结构和对非极性突变体的分析,对参与核心生物合成的基因的功能提出了建议。