Godio Ramiro P, Martín Juan F
Area de Microbiología, Departamento de Biología Molecular, Facultad de CC. Biológicas y Ambientales, Universidad de León, Campus de Vegazana s/n, León, Spain.
Fungal Genet Biol. 2009 Mar;46(3):232-42. doi: 10.1016/j.fgb.2008.12.002. Epub 2008 Dec 24.
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 oxidosqualene 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 oxidosqualene cyclase specific for secondary metabolite biosynthesis; this is in agreement with the finding of two squalene cyclases in the sequenced genomes of basidiomycetes.
砖红韧伞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鲨烯环化酶（occ）的基因，该酶参与氧化鲨烯向棒酸的转化。通过基因替换破坏occ基因的突变体无法合成棒酸，但生长不需要甾醇。occ基因的扩增使棒酸产量提高了35 - 67%。对occ基因表达的Northern分析证实，occ表达与棒酸生物合成之间存在明显的相关性。对occ编码的氧化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，存在一种对次生代谢物生物合成具有特异性的氧化鲨烯环化酶；这与担子菌测序基因组中发现的两种鲨烯环化酶的结果一致。
