摘要
微生物产生众多结构和生物活性多样的次级代谢产物,其生物合成基因簇的克隆是药物创新和产量提高的必要前提。迄今为止已有超过150种生物合成基因簇通过各种方式被克隆,并被用于组合生物合成、体外糖类随机化、代谢工程的定向改造。我们研究室已经克隆并测定了氨基糖苷类井冈霉素/有效霉素、多烯类抗生素FR-008/克念菌素、聚醚类南昌霉素、聚酮类梅岭霉素、杂合聚酮-多肽类口恶唑霉素等生物合成基因簇。深入的基因功能分析揭示了他们独特的生物合成途径和调节机理,为正在进行的组合生物合成结构改造和代谢工程产量提高奠定了基础。
Microorganisms produce myriads of secondary metabolites with both structural and functional diversities. The cloning of corresponding biosynthetic gene clusters is essential for new drug discovery and yield improvement by metabolic engineering. To date, more than 150 biosynthetic gene clusters had been cloned via different strategies, which are subsequently manipulated through combinatorial biosynthesis, in vitro glycorandomization, or other biotechnological methods. In our laboratory, several biosynthetic gene clusters have been cloned and sequenced, representatives of which are responsible for the biosyntheses of the aminoglycoside jinggangmycin/validamycin, polyene antibiotic FR-008/candicidin, polyether nanchangmycin, polyketide meilingmycin, PKS-NRPS oxazomycin and others. Extensive analyses of gene functions, their unique biosynthetic pathways and regulatory mechanisms have now paved the way for more rational structural modifications through combinatorial biosynthesis and yield improvements using metabolic engineering.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2006年第2期80-86,99,共8页
Chinese Journal of Antibiotics
关键词
微生物次级代谢产物
生物合成基因簇
药物创新
组合生物合成
代谢工程
Microbial secondary metabolites
Biosynthetic gene cluster
New drug discovery
Combinatorial biosynthesis
Metabolic engineering
