Modified oxidosqualene cyclases in the formation of bioactive secondary metabolites: Biosynthesis of the antitumor clavaric acid
Modified oxidosqualene cyclases in the formation of bioactive secondary metabolites: Biosynthesis of the antitumor clavaric acid
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DOI：
10.1016/j.fgb.2008.12.002
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发表时间：
2009-03-01
影响因子：
3
通讯作者：
Martin, Juan F.
中科院分区：
文献类型：
--
作者：
Godio, Ramiro P.;Martin, Juan F.
Hypholoma sublateritium是一种能产生抗肿瘤化合物棒酸的担子菌。我们克隆了一个编码氧化角鲨烯环化酶（occ）的基因，该酶参与氧化角鲨烯向克拉瓦酸的转化。通过基因替换破坏occ的突变体不能合成克拉瓦酸，但生长不需要甾醇。occ基因的扩增使克拉瓦酸产量增加了35-67%。对occ基因表达的北方分析证实，occ表达与克拉瓦酸生物合成存在明显的相关性。对occ编码的氧化角鲨烯环化酶的分析表明，它具有VSDCVGE基序，而不是活性中心的共有VSDCTAE序列。总之，有一个氧化鲨烯环化酶的次级代谢产物的生物合成特异性，这是在一致的发现两个角鲨烯环化酶的测序基因组中的担子菌。(C)2008年爱思唯尔公司All rights reserved.
Hypholoma sublateritium is a basidiomycete that produces the antitumor compound clavaric acid. We cloned a gene encoding an oxidosqualene cyclase (occ) that is involved in the conversion of oxiclosqualene to clavaric acid. Mutants disrupted in occ by gene replacement were unable to synthesize clavaric acid, but did not require sterols for growth. Amplification of the occ gene produced a 35-67% increase in clavaric acid yield. Northern analysis of occ gene expression confirmed that there is a clear correlation of occ expression and clavaric acid biosynthesis. Analysis of the occ-encoded oxidosqualene cyclase revealed that it has VSDCVGE motif instead of the consensus VSDCTAE sequence of the active center. In summary, there is an oxiclosqualene cyclase specific for secondary metabolite biosynthesis; this is in agreement with the finding of two squalene cyclases in the sequenced genomes of basidiomycetes. (C) 2008 Elsevier Inc. All rights reserved.