理性设计的甘化甲基素:使用来自三个不同的生物合成途径的基因的混合芳香多基基基因
Axel Trefzer1, Gloria Blanco, Lily Remsing
1Albert-Ludwigs-Universität Freiburg im Breisgau, Pharmazeutische Biologie, Stefan-Meier Strasse 19, 79104 Freiburg, Germany.
Journal of the American Chemical Society
|May 23, 2002
概括
研究人员通过在Streptomyces argillaceus中表达urdGT2基因来设计新的C-糖基化分子. 这一突破证明了C-glycosyltransferase UrdGT2的存在.
科学领域:
- 合成生物学 合成生物学
- 自然产品的生物合成.
- 葡萄糖化学 葡萄糖化学
背景情况:
- 米特拉米和乌尔达米是具有治疗潜力的复杂多基基.
- 糖基化显著影响这些化合物的生物活性.
- 了解甘氨基转移酶的功能对于设计新型类似物至关重要.
研究的目的:
- 为了研究C-glycosyltransferaseUrdGT2.2.的基质灵活性.
- 通过使用异构表达来设计新型C-糖基化密拉米类分子.
- 探索组合生物合成,以创建混合糖化物结构.
主要方法:
- 来自Streptomyces fradiae的urdGT2基因在工程化Streptomyces argillaceus突变体中的异构表达.
- 在S. argillaceus突变体中,来自不同类型链球菌的urdGT2和lanGT1基因的同时表达.
- 使用分析技术阐明新型C-糖基化化合物的结构.
主要成果:
- 生产了四种新的C-糖基化米素类型分子,包括9-C-olivosylpremithramycinone和9-C-mycarosylpremithramycinone.
- 一个新的混合分子,9-C-(olivo-1-4-olivosyl) -premithramycinone,通过三种不同的生物体的共同表达基因来合成.
- 证明了UrdGT2对糖供体和接受体的广泛基质耐受性,以及在先前未糖化位置的糖化.
结论:
- 在C-glycosyltransferase UrdGT2表现出显著的基质灵活性.
- 产生了具有新生物活动潜力的新型混合分子.
- 组合生物合成是设计和生产复杂的甘油化天然产品的可行策略.
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