逆向代谢工程的最新研究进展

Progress in inverse metabolic engineering

摘要:

随着高通量测序技术的快速发展，可以快速地通过基因组尺度的序列比较，来全面、系统地探讨工业生产菌株和实验室优良菌株的遗传基础，分析基因型-表型之间的关系；同时结合准确的基因组修饰技术，完成基于全基因组突变分析的逆向代谢工程。近年来，基于全基因组突变分析的逆向代谢工程已经成功地应用于微生物优良菌株选育，成为了研究的前沿和热点。综述了近几年逆向代谢工程发展的研究方法，突变型-表型相关性分析，逆向代谢工程的最新进展及其应用，并讨论其面临的问题及挑战。

关键词:逆向代谢工程，基因型，表型，重构

Abstract:

In the last few years, high-throughput (or ‘next-generation’) sequencing technologies have delivered a step change in our ability to sequence genomes, whether human or bacterial. Further comparative genome analysis enables us to reveal detailed knowledge of genetics or physiology of industrial important strains obtained in laboratory, to analyze genotype-phenotype correlations of mutants with improved performance. Based on identified key mutations or mutation combinations, Inverse Metabolic Engineering (IME) can be performed by using accurate genetic modification system. Recently, IME has been successfully used for strain improvement and has become a research hotspot, including improving substrate utilization, engineering the robustness of industrial microbes and enhancing production of bio-based products. Here, we describe recent advances in research methods of IME, with an emphasis on characterization of genotype-phenotype and the latest advances and application of IME. Possible directions and challenges for further development of IME are also discussed.

Key words:inverse metabolic engineering, genotype, phenotype, reconstruction