Biosynthetic Mechanism of Unique Lipids Constituting Archaebacterial Cell-Membrane

进化上耐人寻味的古细菌含有2，3-二微米聚异丙基甘油结构作为核心膜脂类，这可以被认为是真细菌和真核细胞类脂的镜像。在本项目中，通过稳定同位素示踪技术和核磁共振分析，研究了提供这种有趣的膜脂立体化学的生物合成机理。1)通过从D-甘露醇合成1，2-和2，3-二微米-植酸甘油的对映专一性合成和对它们的500 MHz~1H-核磁共振波谱的仔细分析，证实了嗜盐古细菌Halbacterium halobium中核心脂类的甘油部分的绝对立体化学。2)首次从化学的角度阐明了2，3-二-欧米隆-植酸甘油的生物合成。核心脂似乎是由甘油和D-葡萄糖通过还原二羟丙酮磷酸或其衍生物生物合成的，在此过程中S…C-2的更多的空间化学是颠倒的。在醚键形成中，甘油的C-2和C-3氧原子起亲核作用。3)基于手性转录的概念，以1，2：5，6-di-OMICRON-iopropylidene-alpha-D-ribo-hexofuranos-3-urose为模板，建立了一种新的简便的手性一氢化甘油的合成方法。4)首次通过追逐D-[5-^2H]-和D-[4-^2H]葡萄糖在盐生盐杆菌核心脂生物合成过程中的氢，并与合成的sn-2进行了500 MHz^1H-核磁共振比较，首次阐明了古细菌磷酸三糖异构酶反应的立体化学。5)发现嗜热嗜酸考古细菌Sulfolobus acidocaldarius的二甘油四醚脂是由甘油生物合成的，而不是在C-2上反转构型，这表明有可能直接形成甘油-1-磷酸，而不是在盐藻中发现的甘油-3-磷酸。一种多样化和不同的生化转变可能在古细菌物种中进化。较少

Evolutionary intriguing archaebacteria contain 2, 3-di-OMICRON-polyisopranyl glycerol structures as core membrane lipids, which may be regarded as mirror images to the lipids of the eubacterial and eukaryotic cells. In this project, the biosynthetic mechanisms which afford such intriguing stereochemistry of the membrane lipids were studied by the stable isotope-tracer technique and NMR analysis.1) The absolute stereochemistry of the glycerol moiety of core lipid in halophilic archaebacteria Halobacterium halobium was confirmed by combination of the enantiospecific synthesis of both 1, 2- and 2, 3-di-OMICRON-phytanyl glycerol from D-mannitol and close analysis of their 500MHz ^1H-NMR spectra.2) The biosynthesis of 2, 3-Di-OMICRON-phytanyl glycerol in H. halobium has been elucidated for the first time from the stereochemical viewpoints. The core lipid appears to be biosynthesized from glycerol and D-glucose via reduction of dihydroxyacetone phosphate or its derivative, during which the s … More tereochemistry of C-2 is inverted. In the ether-bond formations, the C-2 and C-3 oxygen atoms of glycerol act as nucleophile. The plausible pathway of the biosynthesis was postulated.3) A novel and convenient synthetic method of chirally monodeuterated glycerol was developed based on the chirality transcription concept using 1, 2 : 5, 6-di-OMICRON-iopropylidene-alpha-D-ribo-hexofuranos-3-urose as a template.4) Stereochemistry of the archaebacterial triose-phosphate isomerase reaction was elucidated for the first time by chasing the deuterium of D-[5- ^2H]-and D-[4- ^2H]glucose during the core lipid biosynthesis in Halobacterium halobium, followed by 500 MHz ^1H-NMR comparison of the deuterated lipid and the synthetic sn-2, 3-di-OMICRON-phytanyl (3R) - and - (3S) -[3- ^2H_1]glycerol.5) The finding that the diglyceryl tetraether lipid of thermoacidophilic archaebacteria Sulfolobus acidocaldarius is biosynthesized from glycerol without inversion of configuration at C-2 suggests a possibility of direct formation of glycerol-1-phosphate rather than glycerol-3-phosphate found in H. halobium. A diversified and contrasting biochemical transformation may be evolved within the archaebacterial species. Less