title: A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis.
abstract: BACKGROUND
  The fatty acids of anaerobic ammonium oxidizing (anammox) bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway.
  
  
  RESULTS
  Gene clusters encoding enzymes of fatty acid biosynthesis in the anammox bacterium Kuenenia stuttgartiensis and 137 other organisms were analysed and compared in silico to gain further insight into the pathway of (ladderane) fatty acid biosynthesis. In K. stuttgartiensis four large gene clusters encode fatty acid biosynthesis. Next to the regular enzyme complex needed for fatty acid biosynthesis (FASII), the presence of four putative S-adenosyl-methionine (SAM) radical enzymes, two enzymes similar to phytoene desaturases and many divergent paralogues of beta-ketoacyl-ACP synthase (fabF) were unusual. Surprisingly, extensive synteny was observed with FASII gene clusters in the deltaproteobacterium Desulfotalea psychrophila. No ladderane lipids were detected in lipid extracts of this organism but we did find unusual polyunsaturated hydrocarbons (PUHC), not detected in K. stuttgartiensis.
  
  
  CONCLUSIONS
  We suggest that the unusual gene clusters of K. stuttgartiensis and D. psychrophila encode a novel pathway for anaerobic PUFA biosynthesis and that K. stuttgartiensis further processes PUFA into ladderane lipids, in similar fashion to the previously proposed route of ladderane lipid biosynthesis. However, the presence of divergent paralogues of fabF with radically different active site topologies may suggest an alternative pathway where ladderane moieties are synthesised externally and are recruited into the pathway of fatty acid biosynthesis.
authors.affiliation: Department of Microbiology, IWWR, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands. jrattray@nioz.nl
authors.forename: Jayne E
authors.initials: JE
authors.lastname: Rattray
authors.forename: Marc
authors.initials: M
authors.lastname: Strous
authors.forename: Huub J M
authors.initials: HJ
authors.lastname: Op den Camp
authors.forename: Stefan
authors.initials: S
authors.lastname: Schouten
authors.forename: Mike Sm
authors.initials: MS
authors.lastname: Jetten
authors.forename: Jaap S Sinninghe
authors.initials: JS
authors.lastname: Damsté
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002244:Carbon; D020134:Catalytic Domain; D003503:Cyclobutanes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D019143:Evolution, Molecular; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005798:Genes, Bacterial; D023281:Genomics; D008055:Lipids / Q000032:analysis / Q000096:biosynthesis*; D010802:Phylogeny
chemical_list: D001426:Bacterial Proteins; D003503:Cyclobutanes; D005227:Fatty Acids; D008055:Lipids; D002244:Carbon