通过基因挖掘基于alazopeptin生物合成酶的基因挖掘来识别两种不同的立体选择性氨酸5-氧酶
Seiji Kawai1, Kota Moriga1, Warawadee Nirdnoy2
1Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Chemistry (Weinheim an der Bergstrasse, Germany)
|February 17, 2025
概括
研究人员确定了新的酶,氨酸5基酶,这些酶在立体选择性地产生不同形式的5氨酸. 这些酶对于制药合成和发现新的天然产品非常有价值.
科学领域:
- 生物化学和酶学 生物化学和酶学
- 自然产品的生物合成.
- 合成生物学 合成生物学
背景情况:
- 能够实现氨基酸的区域选择性和立体选择性氧化酶对于制药合成至关重要.
- 氨酸5基酶 (AzpK) 涉及alazopeptin生物合成,但其体外活性仍未得到证实.
研究的目的:
- 为了识别和表征氨酸5氧酶,参与5氧氨酸生物合成.
- 探索这些酶在立体选择性合成和天然产品发现中的潜力.
主要方法:
- 阿拉佐佩生物合成基因集群的基因挖掘,以识别α-甲酸/Fe2+依赖的二氧化酶酶.
- 鉴定出的酶 (Am_AzpK2,Pp_AzpK2) 的特征是它们能够合成特定的5-基西林异构体.
- 用于立体化学分析,识别 AzpJ 同类物作为脱酶.
主要成果:
- 两个α-谷酸盐/Fe2+依赖的二氧化酶Am_AzpK2和Pp_AzpK2被确定为氨酸5基酶.
- 这些酶合成了不同的异构体:分别是 (2S,5S) -5-基和 (2S,5R) -5-基.
- 证实AzpJ同类物是立体选择性脱酶,有助于表征5-基素立体化学和酶活性.
结论:
- 这项研究为立体选择性生产5-基氨酸提供了基础技术.
- 基因组扫描发现了额外的氨酸5基酶,这表明存在未被发现的含有5-氨酸的天然产品.
- 对这些立体选择性酶的进一步研究将阐明自然立体选择性氧化过程的机制.
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