物理上离散的β-内酰胺酶型硫酯酶在迭代I型聚酮合酶催化的阿卓醌合成中催化产物释放。

Physically discrete beta-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase.

作者信息

Awakawa Takayoshi, Yokota Kosuke, Funa Nobutaka, Doi Fuminao, Mori Naoki, Watanabe Hidenori, Horinouchi Sueharu

机构信息

Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

出版信息

Chem Biol. 2009 Jun 26;16(6):613-23. doi: 10.1016/j.chembiol.2009.04.004.

DOI:10.1016/j.chembiol.2009.04.004

PMID:19549600

Abstract

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.

摘要

土曲霉中的ATEG_08451，在这里命名为阿托曲松羧酸合酶（ACAS），是一种非还原型迭代I型聚酮合酶，不含硫酯酶结构域。在体外，ACAS与丙二酰辅酶A的反应产生了一种聚酮中间体，可能附着在其酰基载体蛋白（ACP）上。向反应中加入ATEG_08450，在这里命名为阿托曲松羧基ACP硫酯酶（ACTE），导致了源自阿托曲松羧酸的产物的释放，如阿托曲松和内色菌素。ACTE属于β-内酰胺酶超家族，因此似乎是一种新型硫酯酶，负责聚酮生物合成中的产物释放。这些发现表明，ACAS从丙二酰辅酶A合成阿托曲松羧酸的支架，并且ACTE水解ACAS的ACP与中间体之间的硫酯键，以释放阿托曲松羧酸作为反应产物。