摘要
系统梳理了庆大霉素生产菌种育种技术的发展脉络与研究现状。详细比较了传统诱变育种与现代基因工程育种两大技术体系。传统育种方面,物理诱变(紫外线、离子束注入、ARTP技术)与化学诱变通过诱导DNA突变提高菌种产量,其中紫外诱变使摇瓶效价提高34.3%,ARTP诱变使效价从1 547 U/mL提升至2 280 U/mL。现代基因工程领域,基因敲除技术通过阻断特定代谢途径将庆大霉素C1a组分比例从6.5%提升至94.0%;CRISPR/Cas9基因编辑技术实现了对甲基转移酶和糖基转移酶的精准调控;DNA改组技术则通过同源基因重组为开发新型抗生素衍生物提供了技术路径。当前庆大霉素菌种选育已从随机诱变转向理性设计阶段,未来发展方向将聚焦于合成生物学、代谢工程与人工智能预测模型的深度融合,通过全局代谢网络解析实现庆大霉素等次级代谢产物的高效生物制造。
This review systematically outlines the development and current research status of breeding technologies for gentamicin-producing strains,providing a detailed comparison between traditional mutagenesis breeding and modern genetic engineering approaches.In traditional breeding methods,physical mutagenesis(including ultraviolet irradiation,ion beam implantation,and ARTP)and chemical mutagenesis enhance strain yield by inducing DNA mutations.Specifically,UV mutagenesis increases shake-flask titer by 34.3%,while ARTP mutagenesis improves the titer from 1547 U/mL to 2280 U/mL.In modern genetic engineering,gene knockout technology successfully increases the proportion of the gentamicin C1a component from 6.5%to 94.0%by blocking specific metabolic pathways;CRISPR/Cas9 gene editing enables precise regulation of methyltransferases and glycosyltransferases;and DNA shuffling technology provides a pathway for developing novel antibiotic derivatives through homologous gene recombination.The review demonstrates that gentamicin strain breeding has transitioned from random mutagenesis to rational design.Future developments will focus on the deep integration of synthetic biology,metabolic engineering,and AI predictive models to achieve efficient bio-manufacturing of secondary metabolites like gentamicin through global metabolic network analysis.
作者
丁强
向继武
卜峰
谭小芳
谭蓉
杨倩
刘佳鑫
程波
周平
龚波
DING Qiang;XIANG Jiwu;BU Feng;TAN Xiaofang;TAN Rong;YANG Qian;LIU Jiaxin;CHENG Bo;ZHOU Ping;GONG Bo(Yichang Sanxia Pharmaceutical Co.Ltd.,Yichang 443000,China;School of Environmental Ecology and Biological Engineering,Wuhan Institute of Technology,Wuhan 430205,China;Hubei Provincial Institute for Veterinary Drug Control,Wuhan 430070,China)
出处
《武汉工程大学学报》
2025年第6期641-646,共6页
Journal of Wuhan Institute of Technology
基金
湖北省重点研发计划项目(2023BBB120)。
关键词
庆大霉素
诱变选育
基因工程
gentamicin
mutagenesis breeding
genetic engineering
