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用于构建人类病原体荚膜多糖的庚糖生物合成的代谢途径。

Metabolic Pathways for the Biosynthesis of Heptoses Used in the Construction of Capsular Polysaccharides in the Human Pathogen .

机构信息

Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.

出版信息

Biochemistry. 2023 Nov 7;62(21):3145-3158. doi: 10.1021/acs.biochem.3c00390. Epub 2023 Oct 27.

DOI:10.1021/acs.biochem.3c00390
PMID:37890137
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10680097/
Abstract

is the leading cause of food poisoning in North America. The exterior surface of this bacterium is coated with a capsular polysaccharide (CPS) that consists of a repeating sequence of 2-5 different carbohydrates that is anchored to the outer membrane. Heptoses of various configurations are among the most common monosaccharides that have been identified within the CPS. It is currently thought that all heptose variations derive from the modification of GDP-d--α-d--heptose (GMH). From the associated gene clusters for CPS biosynthesis, we have identified 20 unique enzymes with different substrate profiles that are used by the various strains and serotypes of to make six different stereoisomers of GDP-6-deoxy-heptose, four stereoisomers of GDP-d--heptoses, and two stereoisomers of GDP-3,6-dideoxy-heptoses starting from d-sedoheptulose-7-phosphate. The modification enzymes include a C4-dehydrogenase, a C4,6-dehydratase, three C3- and/or C5-epimerases, a C3-dehydratase, eight C4-reductases, two pyranose/furanose mutases, and four enzymes for the formation of GMH from d-sedoheptulose-7-phosphate. We have mixed these enzymes in different combinations to make novel GDP-heptose modifications, including GDP-6-hydroxy-heptoses, GDP-3-deoxy-heptoses, and GDP-3,6-dideoxy-heptoses.

摘要

是导致北美食物中毒的主要原因。这种细菌的外表面覆盖着一层荚膜多糖 (CPS),由 2-5 种不同碳水化合物的重复序列组成,锚定在外膜上。各种构型的庚糖是已在 CPS 中鉴定出的最常见的单糖之一。目前认为,所有庚糖变异都源自 GDP-d--α-d--庚糖 (GMH) 的修饰。从 CPS 生物合成的相关基因簇中,我们已经鉴定出 20 种具有不同底物特征的独特酶,这些酶被不同株系和血清型的 用来从 d-景天庚酮糖-7-磷酸生成六种不同的 GDP-6-脱氧庚糖立体异构体、四种 GDP-d--庚糖立体异构体和两种 GDP-3,6-二脱氧庚糖立体异构体。修饰酶包括 C4-脱氢酶、C4,6-脱水酶、三个 C3 和/或 C5-差向异构酶、C3-脱水酶、八个 C4-还原酶、两个吡喃糖/呋喃糖变位酶和四个将 d-景天庚酮糖-7-磷酸转化为 GMH 的酶。我们将这些酶以不同的组合混合,以生成新型 GDP-庚糖修饰物,包括 GDP-6-羟基庚糖、GDP-3-脱氧庚糖和 GDP-3,6-二脱氧庚糖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/e40ff929b830/bi3c00390_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/faa58d4d8a99/bi3c00390_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/89ebedf1e30a/bi3c00390_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/c86833a722e8/bi3c00390_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/e40ff929b830/bi3c00390_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/faa58d4d8a99/bi3c00390_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/89ebedf1e30a/bi3c00390_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/c86833a722e8/bi3c00390_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb1/10862484/e40ff929b830/bi3c00390_0007.jpg

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