Physically discrete beta-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase.
ATEG_08451 in Aspergillus terreus, here named atrochrysone carboxylic acid synthase (ACAS), is a nonreducing, iterative type I polyketide synthase that contains no thioesterase domain. In vitro, reactions of ACAS with malonyl-CoA yielded a polyketide intermediate, probably attached to its acyl carrier protein (ACP). The addition of ATEG_08450, here named atrochrysone carboxyl ACP thioesterase (ACTE), to the reaction resulted in the release of products derived from atrochrysone carboxylic acid, such as atrochrysone and endocrocin. ACTE, belonging to the beta-lactamase superfamily, thus appears to be a novel type of thioesterase responsible for product release in polyketide biosynthesis. These findings show that ACAS synthesizes the scaffold of atrochrysone carboxylic acid from malonyl-CoA, and that ACTE hydrolyzes the thioester bond between the ACP of ACAS and the intermediate to release atrochrysone carboxylic acid as the reaction product.
Awakawa
Takayoshi
T
Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Yokota
Kosuke
K
Funa
Nobutaka
N
Doi
Fuminao
F
Mori
Naoki
N
Watanabe
Hidenori
H
Horinouchi
Sueharu
S
D000213:Acyl Carrier Protein / Q000378:metabolism; D000873:Anthracenes / Q000737:chemistry / Q000378:metabolism*; D000880:Anthraquinones / Q000378:metabolism; D001230:Aspergillus / Q000201:enzymology; D002384:Catalysis; D008316:Malonyl Coenzyme A / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013869:Thiolester Hydrolases / Q000378:metabolism*; D001618:beta-Lactamases / Q000378:metabolism
D000213:Acyl Carrier Protein; D000873:Anthracenes; D000880:Anthraquinones; C543415:atrochrysone; C023523:endocrocin; D008316:Malonyl Coenzyme A; D048630:Polyketide Synthases; D013869:Thiolester Hydrolases; D001618:beta-Lactamases