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在酵母中通过Norlaudanosoline产生基素化物提高了滴度,选择性和产量

Lauren Narcross^1,2, Michael E Pyne^1,2, Kaspar Kevvai^1,2

¹Department of Biology, Concordia University, Montréal, Québec H4B 1R6, Canada.

ACS synthetic biology

|March 4, 2026

概括

研究人员开发了一种新的微生物合成路径,用于基素化物 (BIA),实现更高的产量 (S) - 网红素和相关化合物,如血红素. 这种进步提高了获得有价值的药品和抗生素的机会.

科学领域:

生物技术和代谢工程生物技术和代谢工程
合成生物学合成生物学
自然产品化学自然产品化学

背景情况:

基素类化合物 (BIAs),包括像吗啡这样的药品和像血红素这样的抗生素,是有价值的化合物,已知成员超过2500.
目前的农业生产方法限制了对BIA的更广泛的访问,阻碍了进一步的研究和商业化.
微生物合成为BIA生产提供了一个可扩展和具有成本效益的替代方案,因为它具有基因可处理性和使用廉价原料.

研究的目的:

为关键的BIA中间体 (S) - 网红素建立一个优越的微生物合成途径.
提高酵母中BIA生产的选择性和效率.
扩展已开发的合成其他高价值BIAs的途径,如血.

主要方法:

设计了酵母代谢路径用于 (S) - 网红素合成,从4-基乙 (4-HPAA) 转换为3,4-二基乙 (3,4-dHPAA) 作为关键中间体.
利用单胺氧化酶A (MAO) 产生3,4-dHPAA,提高途径选择性并减少目标外的四化 (THIQ) 副产品.
进行料批发发酵以优化 (S) - 网红素的标位和产量,随后进行二血氨酸/血氨酸.

主要成果:

获得了4.8g/L (S) - 网红素的标位,超过了以前的产量超过40% (从17到24mg/g的糖).
新的 (S-norlaudanosoline) 路径显示了增强的选择性,减轻了随性酶活性的问题.
成功产生了635mg/L的二血素和血素,比之前报告的微生物标位增加了40倍.

结论:

使用3,4-dHPAA的新型微生物途径代表了 (S) - 网红素的高效和选择性生产的重大进展.
这种工程途径为多样化和有价值的BIAs的可扩展生物合成提供了一个强大的平台.
获得的高血红素和二血红素位为它们的商业生产和治疗应用开辟了新的途径.

关键词:

这种植物是Saccharomyces cerevisiae.基化素化物基化代谢工程是代谢工程.网红素是什么意思网红素是什么意思合成生物学合成生物学酵母酵母是一种酵母.

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