酿酒酵母 ERG11/CYP51（甾醇 14α-脱甲基酶）强力霉素调控突变体的互补作用和烟曲霉同工酶 CYP51A 和 CYP51B 的唑类敏感性筛选。
Complementation of a Saccharomyces cerevisiae ERG11/CYP51 (sterol 14α-demethylase) doxycycline-regulated mutant and screening of the azole sensitivity of Aspergillus fumigatus isoenzymes CYP51A and CYP51B.
机构信息
Institute of Life Science and School of Medicine, Swansea University, Swansea, Wales, United Kingdom.
出版信息
Antimicrob Agents Chemother. 2010 Nov;54(11):4920-3. doi: 10.1128/AAC.00349-10. Epub 2010 Aug 23.
Abstract
Aspergillus fumigatus sterol 14α-demethylase isoenzymes CYP51A and CYP51B were heterologously expressed in a Saccharomyces cerevisiae mutant (YUG37-erg11), wherein native ERG11/CYP51 expression is controlled using a doxycycline-regulatable promoter. When cultured in the presence of doxycycline, recombinant YUG37-pcyp51A and YUG37-pcyp51B yeasts were able to synthesize ergosterol and grow; a control strain harboring reverse-oriented cyp51A could not. YUG37-pcyp51A and YUG37-pcyp51B constructs showed identical sensitivity to itraconazole, posaconazole, clotrimazole, and voriconazole. Conversely, YUG37-pcyp51A withstood 16-fold-higher concentrations of fluconazole than YUG37-pcyp51B (8 and 0.5 μg ml⁻¹, respectively).
摘要
烟曲霉甾醇 14α-脱甲基酶同工酶 CYP51A 和 CYP51B 在酿酒酵母突变体（YUG37-erg11）中异源表达，其中天然 ERG11/CYP51 的表达受强力霉素可调控启动子控制。当在强力霉素存在下培养时，重组 YUG37-pcyp51A 和 YUG37-pcyp51B 酵母能够合成麦角固醇并生长；而含有反向定向 cyp51A 的对照菌株则不能。YUG37-pcyp51A 和 YUG37-pcyp51B 构建体对伊曲康唑、泊沙康唑、克霉唑和伏立康唑的敏感性相同。相反，YUG37-pcyp51A 能耐受比 YUG37-pcyp51B 高 16 倍的氟康唑浓度（分别为 8 和 0.5 μg ml⁻¹）。
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