通过新发现的酶级联合成多种麻黄类生物碱

Q2 Agricultural and Biological Sciences
生物设计研究(英文) Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI:10.34133/bdr.0048
Peiling Wu, Ding Luo, Yuezhou Wang, Xiaoxu Shang, Binju Wang, Xianming Deng, Jifeng Yuan
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引用次数: 0

摘要

麻黄类生物碱是一大类天然和合成的苯丙羟胺分子,具有极高的药用价值。然而,现有的方法通常依赖化学方法对麻黄类生物碱的 N 基进行多样化修饰。在此,我们报告了一种分两步进行的酶组装生产线,用于制造结构多样化的麻黄类生物碱,以取代传统的化学修饰步骤。我们首先从枯草芽孢杆菌(BsAlsS,乙酰乳酸合成酶)中发现了一种新的碳酰化酶,它是一种强大的催化剂,能从不同的芳香醛中生成不同的苯乙酰基卡宾醇(PAC)类似物,转化率接近 100%。随后,我们筛选了亚胺还原酶(IREDs)用于 PAC 类似物的还原胺化。结果发现,来自白化链霉菌的 IRG02 具有良好的活性,在与烯丙基胺、丙炔基胺和环丙基胺等不同胺伙伴进行还原性烷基化反应时,转化率从 37% 到 84% 不等。总之,我们在麻黄类生物碱的 N 基上建立了 3 种新的生物改性。综上所述,我们的研究工作为今后利用生物催化合成结构多样的麻黄类生物碱奠定了基础,并具有潜在的新医药应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biosynthesis of Diverse Ephedra-Type Alkaloids via a Newly Identified Enzymatic Cascade.

Ephedra-type alkaloids represent a large class of natural and synthetic phenylpropanolamine molecules with great pharmaceutical values. However, the existing methods typically rely on chemical approaches to diversify the N-group modification of Ephedra-type alkaloids. Herein, we report a 2-step enzymatic assembly line for creating structurally diverse Ephedra-type alkaloids to replace the conventional chemical modification steps. We first identified a new carboligase from Bacillus subtilis (BsAlsS, acetolactate synthase) as a robust catalyst to yield different phenylacetylcarbinol (PAC) analogs from diverse aromatic aldehydes with near 100% conversions. Subsequently, we screened imine reductases (IREDs) for the reductive amination of PAC analogs. It was found that IRG02 from Streptomyces albidoflavus had good activities with conversions ranging from 37% to 84% for the reductive alkylamination with diverse amine partners such as allylamine, propargylamine, and cyclopropylamine. Overall, 3 new bio-modifications at the N-group of Ephedra-type alkaloids were established. Taken together, our work lays a foundation for the future implementation of biocatalysis for synthesizing structurally diverse Ephedra-type alkaloids with potential new pharmaceutical applications.

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来源期刊
CiteScore
3.90
自引率
0.00%
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审稿时长
12 weeks
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