In most bacteria Selleck ISRIB the role of introducing acyl chain disorder is fulfilled by unsaturated fatty acids (UFAs). Some bacteria synthesize UFA by desaturation, an oxygen-requiring reaction that introduces the double bond in a single concerted reaction [2]. However, as first recognized

by Bloch and coworkers this is not an option for anaerobically grown bacteria [3]. These investigators originally proposed that introduction of the double bond involved a direct dehydration of the 3-hydroxydecanoyl intermediate of fatty acid synthesis to give a cis-3 double bond which would be conserved though subsequent cycles of addition of two carbon atoms to give the membrane lipid UFA moieties [4]. However, when tested in cell-free extracts of E. coli, the reaction proved to proceed by a more conservative dehydration to give the classical trans-2-decenoyl fatty acid synthetic intermediate followed by isomerization of the

trans-2-double bond to the cis-3 species [3, 5]. This cis double bond was then preserved through successive C2 elongation cycles to form the double bond of the mature UFAs [6, 7]. The dehydration and isomerization reactions were demonstrated by purification of the E. coli FabA enzyme (called the “”Bloch dehydratase”" to distinguish it from the E. coli FabZ dehydratase of the elongation cycle) that catalyzed both the dehydration and isomerization reactions(Fig. selleck compound PRKACG 1) [5]. Ironically, although the pathway was originally proposed based on the patterns of incorporation of short chain radioactive fatty acids into UFAs by cultures of Clostridium butyricum (now Clostridium beijerinckii) [4], all of the extant Clostridial genomes lack a homologue of FabA, the E. coli dehydratase-isomerase studied by Bloch

and coworkers. Indeed, many bacterial genomes do not encode a recognizable FabA. This is also true of FabB, the E. coli chain elongation enzyme that channels the metabolic intermediate produced by FabA into the mainstream fatty acid synthetic pathway. Indeed in the extant genome sequences FabA and FabB homologues are encoded only in the genomes of α- and γ-proteobacteria [6, 7]. Thus far, two MLN4924 manufacturer solutions that solve the problem of anaerobic UFA synthesis in the absence of FabA and FabB have been reported. The first solution was that of Streptococcus pneumoniae which introduces a cis double bond into the growing acyl chain using FabM, a trans-2 to cis-3-decenoyl-ACP isomerase (i.e., the second partial reaction of FabA) [8]. The second solution was that of Enterococcus faecalis which uses homologues of FabZ and FabF to perform the functions performed by FabA and FabB in E. coli [9]. E. faecalis encodes two FabZ homologues and two FabF homologues (FabF is closely related to FabB).