通过在微乳液系统中代谢工程Mycobacterium neoaurum将植物转化为双醇的高效生物转化
Xinxin Wang1,2, Xia Ke1,2, Hongduo Dong1,2
1National and Local Joint Engineering Research Center for Biomanufacturing of Choral Chemicals, Zhejiang University of Technology, Hangzhou, People's Republic of China.
Biotechnology journal
|September 19, 2024
概括
研究人员开发了一种新的微生物方法来生产4-HBC (21-Hydroxy-20-methylpregn-4-en-3-one),这是一个关键的类固醇药物中间体. 这种改进的生物转化途径和基质系统从植物中获得了高产量.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 微生物化学 微生物化学
背景情况:
- 21-Hydroxy-20-methylpregn-4-en-3-one (4-HBC) 是合成类固醇药物的重要中间体.
- 目前从植物醇中合成4-HBC的微生物合成面临诸如副产品形成和基质溶解性差等挑战.
- 工业4-HBC生产需要高效的生物转化途径和基质系统.
研究的目的:
- 为4-HBC合成设计一种直接的生物转化途径.
- 开发一种高效的基质乳液系统,以提高生物可用性.
- 为了优化从植物醇中产生4-HBC的微生物生产.
主要方法:
- 鉴定并描述了来自Mycobacterium neoaurum.com的新型异酶KstD4,KstD5 (3-ketosteroid-Δ1-dehydrogenase) 和KsHA3 (3-ketosteroid 9α-hydroxylase) 的特性.
- 通过基因删除和增强胆固醇氧化酶 (ChOx2) 和-CoA酸酶 (EchA19) 的表达,代谢工程化了Mycobacterium neoaurum菌株.
- 开发了一个微乳液系统,使用大豆油和xypropyl-β-cyclodextrin来提高基质溶解度.
主要成果:
- 实现了用于4HBC合成的直接生物转化途径.
- 设计的菌株和乳液系统显著提高了基质的溶解性和生物可用性.
- 批发发酵从50g/L的植物中产生39.5g/L的4-HBC,其摩尔产量为96.7%.
结论:
- 成功设计了一种代谢强大的菌株,用于直接生物合成4-HBC.
- 开发的微乳液系统增强了基质的利用,用于微生物的转化.
- 这项研究表明,对工业规模的4-HBC.生物合成有前途的战略.
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