Aspergillus oryzae type III polyketide synthase CsyA is involved in the biosynthesis of 3,5-dihydroxybenzoic acid.
As a novel superfamily of type III polyketide synthases in microbes, four genes csyA, csyB, csyC, and csyD, were found in the genome of Aspergillus oryzae, an industrially important filamentous fungus. In order to analyze their functions, we carried out the overexpression of csyA under the control of alpha-amylase promoter in A. oryzae and identified 3,5-dihydroxybenzoic acid (DHBA) as the major product. Feeding experiments using (13)C-labeled acetates confirmed that the acetate labeling pattern of DHBA coincided with that of orcinol derived from orsellinic acid, a polyketide formed by the condensation and cyclization of four acetate units. Further oxidation of methyl group of orcinol by the host fungus could lead to the production of DHBA. Comparative molecular modeling of CsyA with the crystal structure of Neurospora crassa 2'-oxoalkylresorcylic acid synthase indicated that CsyA cavity size can only accept short-chain acyl starter and tetraketide formation. Thus, CsyA is considered to be a tetraketide alkyl-resorcinol/resorcylic acid synthase.
Seshime
Yasuyo
Y
School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan.
Juvvadi
Praveen Rao
PR
Kitamoto
Katsuhiko
K
Ebizuka
Yutaka
Y
Nonaka
Takamasa
T
Fujii
Isao
I
D001236:Aspergillus oryzae / Q000201:enzymology*; D003198:Computer Simulation; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012118:Resorcinols
D005656:Fungal Proteins; D062385:Hydroxybenzoates; D012118:Resorcinols; C076950:alpha-resorcylic acid; D048630:Polyketide Synthases