London Research and Development Center, Agriculture and Agri-Food Canada, London, ON N5V 4T3, Canada.
Department of Biology, Western University, London, ON N6A 3K7, Canada.
Toxins (Basel). 2024 Sep 19;16(9):404. doi: 10.3390/toxins16090404.
Zearalenone and radicicol are resorcylic acid lactones produced by numerous plant pathogenic fungi. Zearalenone is a non-steroidal estrogen mimic that can cause serious reproductive issues in livestock that consume contaminated feed. Radicicol is a potent inhibitor of the molecular chaperone Hsp90, which, in plants, has an important role in coordinating the host's immune response during infection. Here, we describe the identification and characterization of a soil-borne strain of the Gram-positive bacterium sp. capable of hydrolyzing the macrolide ring of resorcylic acid lactones, including zearalenone and radicicol. Proteomic analysis of biochemically enriched fractions from the isolated and cultured bacterium identified an α/β-hydrolase responsible for this activity. A recombinantly expressed and purified form of the hydrolase (termed RALH) was active against both zearalenone and radicicol. Interpretation of high-resolution mass spectrometry and NMR data confirmed the structures of the enzymatic products as the previously reported non-toxic metabolite hydrolyzed zearalenone and hydrolyzed radicicol. Hydrolyzed radicicol was demonstrated to no longer inhibit the ATPase activity of the Hsp90 homolog in vitro. Enzymatic degradation of resorcylic acid lactones will enable insight into their biological functions.
玉米赤霉烯酮和雷杜霉素是由许多植物病原真菌产生的,resorcylic 酸内酯。玉米赤霉烯酮是一种非甾体雌激素类似物，能导致食用受污染饲料的牲畜产生严重的生殖问题。雷杜霉素是一种有效的分子伴侣 Hsp90 的抑制剂，在植物中，它在协调宿主感染过程中的免疫反应方面起着重要作用。在这里，我们描述了一种土壤传播的革兰氏阳性细菌的鉴定和特征，该细菌能够水解 resorcylic 酸内酯的大环内酯环，包括玉米赤霉烯酮和雷杜霉素。从分离和培养的细菌的生化富集部分的蛋白质组学分析鉴定了一种负责这种活性的α/β-水解酶。该水解酶的重组表达和纯化形式（称为 RALH）对玉米赤霉烯酮和雷杜霉素均具有活性。高分辨率质谱和 NMR 数据分析的解释证实了酶解产物的结构为先前报道的无毒代谢物水解玉米赤霉烯酮和水解雷杜霉素。体外实验表明，水解雷杜霉素不再抑制 Hsp90 同系物的 ATP 酶活性。resorcylic 酸内酯的酶促降解将使人们深入了解它们的生物学功能。
