瓦利诺揭示了在自然界广泛存在的微生物酸盐生物合成的新途径
Yeying Zhang1, Li Chen1, Jake A Wilson1,2
1Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States.
Journal of the American Chemical Society
|May 26, 2022
概括
研究人员发现了瓦林的完整生物合成路径. 这一发现揭示了酸盐天然产品生物合成中的新酶步骤和中间体,扩大了基因组开采潜力.
科学领域:
- 生物化学
- 自然产品生物合成
- 基因组学
背景情况:
- 酸盐天然产品是细胞代谢的重要抑制剂,在医学和生物技术中具有应用.
- 基因组挖掘加速了新型酸盐的发现,但全面的代谢框架对于识别具有理想生物活性的化合物至关重要.
研究的目的:
- 为了阐明瓦利诺的完整生物合成途径,一种含有 (R) -2,3-二基酸 (DHPPA) 支架的酸.
- 在酸盐生物合成中识别新的酶变化和中间体.
主要方法:
- 细菌基因组的生物信息分析,以确定与DHPPA生物合成相关的基因群.
- 用于描述在拟议途径中已识别的酶的功能.
- 代谢标记和结构分析以确认途径中间体.
主要成果:
- 揭示了瓦林的完整生物合成途径,揭示了以前未知的酶步骤和中间体.
- 一种新型脱酶被确定为酸酸突变酶的合酶,通过酸酸盐生物合成创建了一个新的分支点.
- 发现激酶和还原酶可催化类似于糖解和氨酸生物合成的反应,产生甲中间体.
- 显示ATP-Grasp酶将l-valine化为DHPPA,随后进行进一步的氨基酸化以形成DHPPA二.
结论:
- 这项研究确立了酸盐天然产品的新生物合成原理.
- 已识别的DHPPA核心途径在多种细菌基因组中保存,这表明存在大量尚未发现的生物活性酸盐.
- 这些发现为未来针对新型酸盐化合物的基因组挖掘工作提供了明确的框架.
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