Disease relevance of ARAFPS

• A gene disruption construct designed to replace a portion of PKS1 with a hygromycin resistance cassette was transformed into C. resinifera through Agrobacterium tumefaciens-mediated transformation [1].

High impact information on ARAFPS

• PKS1 is interrupted by four apparent introns (74, 57, 49, and 41 bp) and exists in the genome as a single copy surrounded by highly repetitive, A + T-rich DNA [2].
• When PKS1 in race T was inactivated by targeted gene disruption, T-toxin production and high virulence were eliminated, indicating that this PKS is required for fungal virulence [2].
• PKS1, a polyketide synthase (PKS)-encoding gene at Tox1A, and DEC1, a decarboxylase-encoding gene at Tox1B, are necessary for T-toxin production [3].
• 2. We have isolated human genomic DNA clones containing the expressed gene (ARAF1) on the X chromosome and a pseudogene (ARAF2) on chromosome 7p12-q11.21 [4].
• PKS1 null mutants had an albino phenotype, and pigmentation was restored by the addition of scytalone, a melanin pathway intermediate [1].

Biological context of ARAFPS

• The ALM gene transformed the albino mutant (Pks1-) to melanin-producing phenotypes, designated CAL transformants [5].
• The PKS1 gene contains one open reading frame, consisting of 3 exons separated by two short introns [6].
• We have determine the DNA sequence and the transcriptional organization of the PKS1 gene [6].
• The cosmid pAC7, carrying the PKS1 gene, when transformed into the albino mutant restores the wild-type melanin phenotype [6].
• The Nodulisporium sp. pks1 gene sequence and the amino acid sequence deduced from its coding region have been deposited in Genbank under Accession No. AF151533 [7].

Associations of ARAFPS with chemical compounds

• The disruption of PKS1 and restoration of pigmentation with scytalone confirmed the presence of a dihydroxynaphthalene-melanin pathway in C. resinifera [1].
• We previously confirmed that the direct product of Pks1p is 1,3,6,8-tetrahydroxynaphthalene [8].
• Sequence analysis revealed that the PKS1 allele found in the albino contained a single point mutation that resulted in an amino acid change from serine to proline at the 3' end of the beta-ketoacyl synthase motif [9].

Analytical, diagnostic and therapeutic context of ARAFPS

• Sequence analysis demonstrated that this gene is 70% identical to the C. lagenarium pks1 gene [7].

References