Work

Biosynthesis of CDP-α- d -fucofuranose and CDP-β- l -6-deoxy-altrofuranose for the Capsular Polysaccharides of Campylobacter jejuni

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Campylobacter jejuni is a Gram-negative human pathogen and is the most common cause of gastroenteritis in the United States and Europe. C. jejuni expresses a capsular polysaccharide (CPS) that enables the evasion of the host immune response and adherence to host epithelial cells. The various subspecies (serotypes) of C. jejuni are distinguished by their unique CPS repeating units. The repeating trisaccharide in the HS:41 serotype was previously found to contain l -arabinofuranose, 6-deoxy- d - altro -heptofuranose, and a third sugar, which is either d -fucofuranose or 6-deoxy- l -altrofuranose. Genome neighborhood and sequence similarity networks were employed to identify five candidate genes for the biosynthesis of d -fucofuranose and 6-deoxy- l -altrofuranose. Here, it was demonstrated that the biosynthetic pathways for both sugars are initiated by the formation of CDP- d -glucose from CTP and d -glucose-1-phosphate as catalyzed by HS41.21. This product is dehydrated by an NAD + -dependent 4,6-dehydratase (HS41.20) that produces CDP-4-keto-6-deoxy- d -glucose. The third enzyme (HS41.19) was shown to catalyze the inversion of stereochemistry at C3 and C5 using CDP-4-keto-6-deoxy- d -glucose as the substrate. The fourth enzyme (HS41.18) is an NADPH-dependent C4-reductase that catalyzes the formation of CDP- d -fucopyranose from CDP-4-keto-6-deoxy- d -glucose in the absence of the 3,5-epimerase but catalyzes the formation of CDP-6-deoxy- l -altropyranose in the presence of the epimerase. The last enzyme (HS41.17) in the pathway was shown to catalyze the FADH 2 -dependent interconversion of CDP- d -fucopyranose and CDP-6-deoxy- l -altropyranose to CDP- d -fucofuranose and CDP-6-deoxy- l -altrofuranose, respectively. The overall synthesis of the two possible products is governed by the catalytic activity of the epimerase, since the C4-reductase and pyranose–furanose mutase are not affected by the stereochemistry at C5.

Source: Biochemistry

DOI: 10.1021/acs.biochem.5c00296

Authors: Max Errickson Simons, Tamari Narindoshvili, Frank M. Raushel

Institution: Texas A&M University

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: National Institutes of Health, National Institute of General Medical Sciences