A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins
A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins
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DOI：
10.1128/aem.03168-15
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发表时间：
2015-12
影响因子：
4.4
通讯作者：
Jonas Wick;D. Heine;G. Lackner;Mathias Misiek;J. Tauber;H. Jagusch;C. Hertweck;D. Hoffmeister
中科院分区：
文献类型：
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作者：
Jonas Wick;D. Heine;G. Lackner;Mathias Misiek;J. Tauber;H. Jagusch;C. Hertweck;D. Hoffmeister
蜜环菌（蜜环菌）是一种重要的树木病原菌，它能产生多种结构上相关的植物活性和植物毒性天然产物，称为蜜环菌内酯。在它们的生物合成过程中，一些化合物家族的成员经历芳香族部分的单氯化，其生物化学和遗传基础以前是未知的。这是首次对担子菌卤化酶的研究，提出了五个黄素依赖性A。在大肠杆菌中异源产生的Mellea酶（ArmH1至ArmH5）。我们证明，所有五种酶转移一个单一的氯原子的melletamine骨干。在天然产物组装过程中的5倍、安全的生物合成步骤是前所未有的。通常，黄素依赖性卤化酶被分类为作用于游离化合物的酶，而不是那些需要载体蛋白结合受体底物的酶。本研究中表征的酶清楚地转化了游离底物。卤代酶的系统发育分支表明，所有的真菌酶共享一个祖先，并反映了子囊菌和担子菌之间的明显分歧。
ABSTRACT The basidiomycetous tree pathogen Armillaria mellea (honey mushroom) produces a large variety of structurally related antibiotically active and phytotoxic natural products, referred to as the melleolides. During their biosynthesis, some members of the melleolide family of compounds undergo monochlorination of the aromatic moiety, whose biochemical and genetic basis was not known previously. This first study on basidiomycete halogenases presents the biochemical in vitro characterization of five flavin-dependent A. mellea enzymes (ArmH1 to ArmH5) that were heterologously produced in Escherichia coli. We demonstrate that all five enzymes transfer a single chlorine atom to the melleolide backbone. A 5-fold, secured biosynthetic step during natural product assembly is unprecedented. Typically, flavin-dependent halogenases are categorized into enzymes acting on free compounds as opposed to those requiring a carrier-protein-bound acceptor substrate. The enzymes characterized in this study clearly turned over free substrates. Phylogenetic clades of halogenases suggest that all fungal enzymes share an ancestor and reflect a clear divergence between ascomycetes and basidiomycetes.