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在工程酵母中抗癌性icariin的de novo生物合成

Ting An¹, Guangyuan Lin², Yang Liu³

¹Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, Department of Chemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Metabolic engineering

|October 18, 2023

概括

研究人员对酵母进行了改造,以产生伊卡林 (ICA),一种具有抗癌性质的化合物. 这种可持续的微生物生产方法克服了传统植物提取和复杂黄化合物的化学合成的局限性.

科学领域:

生物技术是生物技术.
代谢工程是代谢工程.
合成生物学合成生物学

背景情况:

伊卡林 (ICA) 具有显著的抗癌性质,在营养药和医学中具有价值.
目前获得ICA (植物提取,化学合成) 的方法由于其复杂的结构和自然丰度低,是不可持续的和昂贵的.

研究的目的:

在微生物宿主中阐明和重建完整的icariin生物合成途径.
建立一种可持续且具有成本效益的方法,用于使用人工酵母制造的 de novo icariin 生产.

主要方法:

来自各种植物来源的13个步骤异构的icariin生物合成途径的阐明.
通过删除或过度表达十个内源基因,对Saccharomyces cerevisiae进行工程.
优化酶局部化 (8-C-prenyltransferase到线粒体) 和表达控制 (特定转移酶的三阶段顺序控制).

主要成果:

在工程酵母中成功合成了icariin的新合成.
在摇瓶条件下达到130μg/L的伊卡里因标位.
建立了迄今为止最长的重建的微生物黄胺路径,从葡萄糖中合成伊卡林.

结论:

证明了可持续的微生物生产复杂的黄类化合物的可行性,如icariin.
提供了传统采购方法的潜在替代方案,使有价值的化合物能够更广泛地获得.
为微生物合成其他复杂的植物衍生分子开辟了道路.

关键词:

葡萄糖基酶化是指葡萄糖基酶化的过程.伊卡里恩是什么意思甲基化甲基化甲基化甲化前化是什么意思这种植物是Saccharomyces cerevisiae.时间空间调节法

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