Disease relevance of fabA

• The FadR protein of E. coli activates transcription of the fabA gene, a key enzyme of fatty acid synthesis [1].
• However, there are a number of anaerobic bacteria whose genomes do not contain a fabA homolog, although these organisms nonetheless produce unsaturated fatty acids [2].
• The Pseudomonas aeruginosa fabA and fabB genes, encoding beta-hydroxyacyl-acyl carrier protein dehydratase and beta-ketoacyl-acyl carrier protein synthase I, respectively, were cloned, sequenced, and expressed in Escherichia coli [3].

High impact information on fabA

• We report that FadR binds to a DNA sequence positioned at -40 relative to the start site of the FadR-regulated fabA transcript (the location favored by positive activators) [1].
• However, the fabA and fabB genes are found only in the Gram-negative alpha- and gamma-proteobacteria, and thus other anaerobic bacteria must synthesize these acids using different enzymes [4].
• A synthetic primer complementary to a portion of the inverted repeat sequences at the ends of the transposon was used to prime DNA synthesis into the flanking fabA sequences [5].
• We demonstrated repression of fadL transcription and activation of fabA transcription in vitro using run-off transcription assays containing purified FadR and RNA polymerase [6].
• Overall, these experiments demonstrated that the affinity of FadR binding for DNA containing the fadB, fadL and fabA promoters was OB > OL1, OL2 > OA [6].

Biological context of fabA

• The FadR-responsive operator within fabA, OA, was localized to a region -47 to -31 base pairs relative to the start of transcription using DNase I protection studies [6].
• Subcloning and physical mapping localized the new gene (called sfa for suppressor of fabA) at 1,070 kb on the E. coli chromosome [7].
• Strains containing both fabB and fadR mutant alleles were constructed and shown to exhibit synthetic lethal phenotypes, similar to those observed in fabA fadR mutants [8].
• Northern analysis demonstrated that fabA and fabB are cotranscribed and most probably form a fabAB operon [3].

Associations of fabA with chemical compounds

• A temperature-sensitive fabA mutant was obtained by site-directed mutagenesis of a single base that induced a G101D change; this mutant grew normally at 30 degrees C but not at 42 degrees C, unless the growth medium was supplemented with oleate [3].

Other interactions of fabA

• The growth phase-dependent increased and decreased transcription of fad genes and fabA, respectively, is dependent on the status of the fadR gene [9].
• The fabR::kan strains had 4- to 8-fold higher levels of fabB and a 2- to 3-fold increase in fabA transcripts as judged by Northern blotting, Affymetrix array analysis, and real-time PCR [10].

References