Schnaitman C A, Klena J D
Department of Microbiology, Arizona State University, Tempe 85287-2701.
Microbiol Rev. 1993 Sep;57(3):655-82. doi: 10.1128/mr.57.3.655-682.1993.
From a historical perspective, the study of both the biochemistry and the genetics of lipopolysaccharide (LPS) synthesis began with the enteric bacteria. These organisms have again come to the forefront as the blocks of genes involved in LPS synthesis have been sequenced and analyzed. A number of new and unanticipated genes were found in these clusters, indicating a complexity of the biochemical pathways which was not predicted from the older studies. One of the most dramatic areas of LPS research has been the elucidation of the lipid A biosynthetic pathway. Four of the genes in this pathway have now been identified and sequenced, and three of them are located in a complex operon which also contains genes involved in DNA and phospholipid synthesis. The rfa gene cluster, which contains many of the genes for LPS core synthesis, includes at least 17 genes. One of the remarkable findings in this cluster is a group of several genes which appear to be involved in the synthesis of alternate rough core species which are modified so that they cannot be acceptors for O-specific polysaccharides. The rfb gene clusters which encode O-antigen synthesis have been sequenced from a number of serotypes and exhibit the genetic polymorphism anticipated on the basis of the chemical complexity of the O antigens. These clusters appear to have originated by the exchange of blocks of genes among ancestral organisms. Among the large number of LPS genes which have now been sequenced from these rfa and rfb clusters, there are none which encode proteins that appear to be secreted across the cytoplasmic membrane and surprisingly few which encode integral membrane proteins or proteins with extensive hydrophobic domains. These data, together with sequence comparison and complementation experiments across strain and species lines, suggest that the LPS biosynthetic enzymes may be organized into clusters on the inner surface of the cytoplasmic membrane which are organized around a few key membrane proteins.
从历史角度来看，脂多糖（LPS）合成的生物化学和遗传学研究始于肠道细菌。随着参与LPS合成的基因片段被测序和分析，这些生物体再次成为研究的焦点。在这些基因簇中发现了许多新的和意想不到的基因，这表明生化途径的复杂性超出了早期研究所预测的范围。LPS研究中最引人注目的领域之一是脂质A生物合成途径的阐明。该途径中的四个基因现已被鉴定和测序，其中三个位于一个复杂的操纵子中，该操纵子还包含参与DNA和磷脂合成的基因。rfa基因簇包含许多LPS核心合成的基因，至少有17个基因。该基因簇中一个显著的发现是一组似乎参与合成替代粗糙核心种类的基因，这些核心种类经过修饰后不能作为O特异性多糖的受体。编码O抗原合成的rfb基因簇已从多种血清型中测序，并表现出基于O抗原化学复杂性所预期的遗传多态性。这些基因簇似乎是通过祖先生物体之间基因片段的交换而产生的。在现已从这些rfa和rfb基因簇中测序的大量LPS基因中，没有一个编码似乎能穿过细胞质膜分泌的蛋白质，令人惊讶的是，编码整合膜蛋白或具有广泛疏水结构域的蛋白质的基因也很少。这些数据，连同跨菌株和物种的序列比较及互补实验，表明LPS生物合成酶可能在围绕少数关键膜蛋白的细胞质膜内表面组织成簇。
