在病毒毒素生物合成中控制多铜氧化酶催化合的固态选择性
Jinyu Hu1, Hang Li1, Yit-Heng Chooi1
1School of Molecular Sciences , University of Western Australia , Perth , Western Australia 6009 , Australia.
Journal of the American Chemical Society
|May 3, 2019
概括
它会产生一种生物活性化合物 - - 病毒毒素. 研究人员确定了控制其合成和立体化学的关键酶VdtB和VdtD,
科学领域:
- * 生物化学和分子生物学
- * 自然产品生物合成
- * 酶学
背景情况:
- 已知Paecilomyces variotii产生生物活性化合物,包括病毒毒素.
- 复杂的自然产品的生物合成通常涉及复杂的酶途径.
- 了解这些途径对于医学和生物技术的潜在应用至关重要.
研究的目的:
- * 阐明 (M) - 病毒毒素及其形体的生物合成途径.
- * 确定和描述负责关键合和立体化学控制步骤的酶.
- * 调查新型贝耶-维利格单氧酶 (BVMO) 在该途径中的功能.
主要方法:
- * 在Aspergillus nidulans中异构途径的重建.
- * 关键酶的鉴定和表征:多铜氧化酶 (VdtB) 和α/β酶类蛋白 (VdtD).
- * 使用重组VdtB和VdtD进行无细胞酶测定以评估催化活性和立体选择性.
- * 一种新的贝耶-维利格单氧酶 (VdtE) 的分析.
主要成果:
- * VdtB被确定为多铜氧化酶,催化半导体毒素的区域选择性6,6'- 合.
- 发现VdtD是一种α/ β酶类蛋白质,可指导病毒毒素产物的轴性性.
- * 复合VdtB和VdtD表明立体选择性合,产生 (M) - 维里迪托克辛及其形体的比例为20:1.
- 发现了一种新型BVMO,VdtE,具有修改产品侧链的能力.
结论:
- * 病毒毒素的生物合成涉及特定的多铜氧化酶 (VdtB) 和控制立体选择性的导体蛋白 (VdtD).
- * 这项研究揭示了在天然产品生物合成中对轴性性进行酶控制的新机制.
- 鉴定出的酶和途径为生物活性化合物的产生提供了洞察力,并为生物工程提供了潜力.
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