Zamir L O, Nikolakakis A, Devor K A, Sauriol F
Centre de Recherche en Microbiologie Appliquée, Université du Québec, Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, Québec, Canada H7V 1B7.
J Biol Chem. 1996 Nov 1;271(44):27353-9. doi: 10.1074/jbc.271.44.27353.
3-Acetyldeoxynivalenol is the major trichothecene produced by the fungus Fusarium culmorum. The first proven tricyclic intermediate in the biosynthesis of 3-acetyldeoxynivalenol has been shown by in vivo studies to be isotrichodermin, a natural metabolite of F. culmorum. Indeed, the feeding of ring-deuterated isotrichodermin resulted in ring-deuterated 3-acetyldeoxynivalenol as shown by NMR studies. In this work, we have shown that the 3-acetyl group of isotrichodermin is mostly lost in its metabolism to 3-acetyldeoxynivalenol. We have shown by two different approaches that the deacetylation occurs at an early step after the first oxygenation step at C-15. Derivatives of isotrichodermin lacking the 3-acetyl such as 3-deacetyl isotrichodermin or 3-oxo-12,13-epoxytrichothec-9-ene are not precursors to 3-acetyldeoxynivalenol. The role of this acetyl exchange mechanism is not clear presently.
3-乙酰脱氧雪腐镰刀菌烯醇是真菌禾谷镰刀菌产生的主要单端孢霉烯族毒素。体内研究表明，3-乙酰脱氧雪腐镰刀菌烯醇生物合成过程中首个经证实的三环中间体是异三孢菌素，它是禾谷镰刀菌的一种天然代谢产物。事实上，如核磁共振研究所示，投喂环氘代异三孢菌素会产生环氘代3-乙酰脱氧雪腐镰刀菌烯醇。在这项研究中，我们发现异三孢菌素的3-乙酰基在其代谢为3-乙酰脱氧雪腐镰刀菌烯醇的过程中大多会丢失。我们通过两种不同方法表明，脱乙酰化发生在C-15首次氧化步骤后的早期阶段。缺乏3-乙酰基的异三孢菌素衍生物，如3-脱乙酰异三孢菌素或3-氧代-12,13-环氧单端孢霉-9-烯，不是3-乙酰脱氧雪腐镰刀菌烯醇的前体。目前尚不清楚这种乙酰交换机制的作用。
