在酸盐生物合成中促进硫迁移和螺旋胺形成的专用黄蛋白
Yuta Tsunematsu1,2, Naoya Maeda1, Michio Sato1
1Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Journal of the American Chemical Society
|December 22, 2020
概括
研究人员发现了一种新型的酶,AclR,它可以在epidithiodiketopiperazines (ETPs) 中产生不寻常的二硫化桥梁. 这种酶
科学领域:
- 生物化学
- 菌群学
- 化学生物学
背景情况:
- 乙二甲酸 (ETP) 是具有生态和药物重要性的环酸.
- 酸是一种来自Aspergillus oryzae的有毒ETP,具有异常的支架,具有环扩大的二硫化物桥梁和螺旋胺系统.
- 这种ETP结构偏差的生物化学基础以前是未知的.
研究的目的:
- 阐明中异常ETP支架的形成背后的生化机制.
- 确定负责独特的碳硫键迁移和螺旋环形成的酶.
- 了解乙化在这些复杂分子生物合成中的作用.
主要方法:
- 在Aspergillus oryzae中进行基因查以确定候选基因.
- 一个ACLR缺乏突变的构建和分析.
- 在体外酶测试以确定AclR的催化活性.
- 结晶学和突变分析的AclR.
- 生物信息分析以确定相关的真菌基因集群.
主要成果:
- 发现了一种新型的氧化还原酶,AclR,催化碳-硫键迁移和螺旋环形成.
- 作为重新排列的先决条件,确定一个神秘的乙化步骤.
- 证明单独AclR促进了硫基迁移,乙基排泄和螺旋胺基的形成.
- 与典型的ETP氧化酶不同,具有非正规的CXXH动机的AclR的硫素氧化酶折叠的特征.
- 发现flavin-adenine dinucleotide (FAD) 支持蛋白质折叠,而不是作为氧化还原因子.
- 作为一种生物信息处理工具,AclR可以发现相关ETP的基因集群.
结论:
- AclR是第一个能够催化碳-硫键迁移和ETP生物合成中的螺旋环形成的酶.
- 这一途径涉及至关重要的密码性乙化步骤.
- AclR 是一种专门的硫氧降解酶家族酶,扩大了ETP的化学多样性.
- 这一发现为复杂的天然产品与异常的二硫化物制剂的生物合成提供了洞察力.
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