Disease relevance of FAS2

• One of the FAS clones ( FAS2 ) produces immunologically cross-reacting material in Escherichia coli [1].
• Molecular structure of the multifunctional fatty acid synthetase gene of Brevibacterium ammoniagenes: its sequence of catalytic domains is formally consistent with a head-to-tail fusion of the two yeast genes FAS1 and FAS2 [2].

High impact information on FAS2

• Balanced levels of subunits alpha and beta are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits [3].
• In this study, we present the nucleotide sequence of the FAS2 gene [4].
• We could not find any sequence homology in the 5' flanking sequence of the FAS1 and FAS2 genes that would suggest common regulatory function [4].
• Regulatory gene INO4 of yeast phospholipid biosynthesis is positively autoregulated and functions as a transactivator of fatty acid synthase genes FAS1 and FAS2 from Saccharomyces cerevisiae [5].
• The role of ACP1 in long-chain fatty acid synthesis was studied in fast and fas2 null mutants completely lacking cytoplasmic fatty acid synthase [6].

Biological context of FAS2

• These data suggest an activating role of subunit beta on FAS2 gene expression or, alternatively, a repression of FAS2 by an excess of its own gene product [7].
• FAS2-lacZ fusion constructs deleted for this region showed high reporter gene expression even in the absence of FAS1, arguing for a negatively-acting downstream repression site (DRS) responsible for FAS1-dependent expression of FAS2 [8].
• Deletion analyses of the regulatory regions of FAS1 and FAS2 revealed common regulatory sequences [9].
• These experiments identify the yeast DNA sequences cloned into 33F1 as originating from the FAS1 gene and those DNA sequences in 102B5, from the FAS2 gene [10].
• Mapping of the trifunctional fatty acid synthetase gene FAS2 on chromosome XVI of Saccharomyces cerevisiae [11].

Associations of FAS2 with chemical compounds

• Previous studies have shown that the genes coding for fatty acid synthase, FAS1 and FAS2, are regulated by inositol (Chirala, S.S. [1992] Proc. Natl. Acad. Sci. USA 89, 10232-10236) [12].
• Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline [3].
• In addition, no differences were noted when comparing the FAS2 sequence, that encompasses the cerulenin-binding domain of FAS, between strain 4918 and two derived cerulenin-resistant (CerR) mutants [13].
• This growth inhibition allowed efficient counter-selection for cells that had undergone homologous recombination between the FAS2 repeats by their growth on galactose medium [14].
• Self-cloning yeast strains containing novel FAS2 mutations produce a higher amount of ethyl caproate in Japanese sake [15].

Physical interactions of FAS2

• Similarly, we also demonstrated the presence of a Reb1p-binding site upstream of FAS2 and its importance for gene activation [16].

Other interactions of FAS2

• Compared to the intact alpha 6 beta 6 complex, the individual FAS subunits synthesized in the delta fas1 or delta fas2 strains exhibit a considerably increased sensitivity towards the proteinases present in the yeast cell homogenate [7].
• The overexpression of FAS1 considerably stimulated MCFA formation while that of ASC2, ACC1 and FAS2 genes was not effective [17].
• However, in contrast to B. ammoniagenes PPT1, this sequence is an integral part of the yeast FAS2 gene [18].

Analytical, diagnostic and therapeutic context of FAS2

• However, site-directed mutagenesis of the respective cis-acting elements upstream of FAS1 and FAS2 revealed that additional sequences activating both genes must exist [16].
• Molecular cloning of the yeast fatty acid synthetase genes, FAS1 and FAS2: illustrating the structure of the FAS1 cluster gene by transcript mapping and transformation studies [1].
• Sequence analysis of this region revealed that the GGT codon encoding Gly-1257 of the FAS2 gene was altered to AGT in the mutant, resulting in the codon for Ser [19].
• Detection of a point mutation in FAS2 gene of sake yeast strains by allele-specific PCR amplification [20].
• Southern blot and sequence analyses confirmed the presence of the FAS2 mutation and the absence of integrated plasmid sequences in the genome of the selected strain [14].

References