title: Unsaturated Fatty Acid Synthesis in the Gastric Pathogen Helicobacter pylori Proceeds via a Backtracking Mechanism.
abstract: Helicobacter pylori is a Gram-negative bacterium that inhabits the upper gastrointestinal tract in humans, and the presence of this pathogen in the gut microbiome increases the risk of peptic ulcers and stomach cancer. H. pylori depends on unsaturated fatty acid (UFA) biosynthesis for maintaining membrane structure and function. Although some of the H. pylori enzymes involved in UFA biosynthesis are functionally homologous with the enzymes found in Escherichia coli, we show here that an enzyme HP0773, now annotated as FabX, uses an unprecedented backtracking mechanism to not only dehydrogenate decanoyl-acyl carrier protein (ACP) in a reaction that parallels that of acyl-CoA dehydrogenase, the first enzyme of the fatty acid β-oxidation cycle, but also isomerizes trans-2-decenoyl-ACP to cis-3-decenoyl-ACP, the key UFA synthetic intermediate. Thus, FabX reverses the normal fatty acid synthesis cycle in H. pylori at the C10 stage. Overall, this unusual FabX activity may offer a broader explanation for how many bacteria that lack the canonical pathway enzymes produce UFA-containing phospholipids.
authors.affiliation: Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China; Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China. Electronic address: hkbi@njmu.edu.cn.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Bi
authors.affiliation: Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China; Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.affiliation: Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China; Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, IL 61801, USA; Department of Biochemistry, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, IL 61801, USA. Electronic address: j-cronan@life.uiuc.edu.
authors.forename: John E
authors.initials: JE
authors.lastname: Cronan
keywords: dehydrogenase; electron acceptor; flavin; isomerase; unsaturated fatty acid symthesis