生物合成安丝菌素的研究进展

doi:10.16085/j.issn.1000-6613.2020-0597

摘要/Abstract

摘要：

安丝菌素（Ansamitocin）是一种微生物来源的美登素类抗生素，具有独特的抗癌活性，其中AP-3在安丝菌素中所占比例最高，是发酵的目标产物，在临床上有靶向治疗乳腺癌的效果，因此具有重要的药用研究价值。但当前AP-3的微生物发酵产量不高，高昂的生产成本制约了其进一步的应用。本文在阐述安丝菌素生物合成及代谢调控机制的基础上，分析讨论了微生物发酵产安丝菌素过程中菌种选育、发酵复杂过程的控制与优化以及下游的分离纯化技术等研究进展。再对未来利用新型诱变技术、合成生物学技术与辅因子工程改造等方法选育高产安丝菌素的工程菌株，以及开发高效创新、低成本的分离纯化工艺进行了展望，以期显著地提高安丝菌素的发酵水平，为工业化安丝菌素的发展奠定坚实的基础。

关键词: 安丝菌素AP-3, 生物合成, 菌种选育, 发酵工艺, 分离纯化

Abstract:

Ansamitocin is a maytansinoid antibiotic from microorganisms, and has extraordinary anti-cancer activity. Ansamitocin P-3 (AP-3) content is maximum during ansamitocins fermentation and it shows strong effects on treatment of breast cancer. However, the low yield of AP-3 limits its commercial application. This review summarizes the biosynthesis and metabolic regulation mechanism of AP-3. Also, the isolation and screening of strains, the control and optimization of fermentation process and separation and purification technology are analyzed and discussed. Meanwhile, we look forward to the methods utilized in the future to screening high-yield strains as well as developing high-efficiency and low-cost separation and purification processes, such as new mutagenesis technology, synthetic biology technology and cofactor engineering, in order to improve the fermentation level and lay a solid foundation of industrialized ansamitocin.

Key words: ansamitocin P-3, biosynthesis, breeding, fermentation process, isolation/purification

中图分类号:

TQ465.5

仲文雅, 俞汶佳, 谷艺明, 郭静, 樊博, 蔡志强. 生物合成安丝菌素的研究进展[J]. 化工进展, 2021, 40(2): 990-997.

Wenya ZHONG, Wenjia YU, Yiming GU, Jing GUO, Bo FAN, Zhiqiang CAI. Progress of ansamitocins by biosynthesis[J]. Chemical Industry and Engineering Progress, 2021, 40(2): 990-997.

图/表 4

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菌株	育种方法	AP-3产量	参考文献
A. pretiosum	紫外诱变+化学诱变	150~370mg/L	[13]
A. pretiosum	基因工程	52mg/L，33mg/L	[14]
A. pretiosumsp. auranticum strainSIPI-3-21	紫外诱变	367mg/L	[20]
A. pretiosumsp. auranticum strainHF-064	常压常温等离子体诱变技术（ARTP）+化学诱变	287mg/L	[21]
A. pretiosumsp. auranticum strainG3-368	化学诱变、原生质体制备与再生+基因组改组技术	132mg/L	[22]
A. pretiosum sp. auranticum ATCC 31565	基因工程	70mg/L	[23]
A. pretiosum	基因工程	246mg/L	[24]
Nocardiopsisansamitocini EGI80425	基因工程	12.6mg/L，7.4mg/L	[25]
A. pretiosumATCC 31280	代谢工程	99mg/L	[26]
A. pretiosumsp. auranticumstrainNXJ-22	代谢工程	141.8mg/L	[27]

菌株	育种方法	AP-3产量	参考文献
A. pretiosum	紫外诱变+化学诱变	150~370mg/L	[13]
A. pretiosum	基因工程	52mg/L，33mg/L	[14]
A. pretiosumsp. auranticum strainSIPI-3-21	紫外诱变	367mg/L	[20]
A. pretiosumsp. auranticum strainHF-064	常压常温等离子体诱变技术（ARTP）+化学诱变	287mg/L	[21]
A. pretiosumsp. auranticum strainG3-368	化学诱变、原生质体制备与再生+基因组改组技术	132mg/L	[22]
A. pretiosum sp. auranticum ATCC 31565	基因工程	70mg/L	[23]
A. pretiosum	基因工程	246mg/L	[24]
Nocardiopsisansamitocini EGI80425	基因工程	12.6mg/L，7.4mg/L	[25]
A. pretiosumATCC 31280	代谢工程	99mg/L	[26]
A. pretiosumsp. auranticumstrainNXJ-22	代谢工程	141.8mg/L	[27]

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