克雷伯氏菌细胞工厂  

Cell factories of Klebsiella spp.

作　　者：郝健[1] HAO Jian(Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China)

机构地区：[1]中国科学院上海高等研究院,上海201210

出　　处：《中国科学：生命科学》2023年第8期1072-1082,共11页Scientia Sinica(Vitae)

基　　金：国家重点研发计划(批准号:2019YFE0196900);上海市自然科学基金(批准号:19ZR1463600);英国皇家学会牛顿高级学者基金(批准号:NAFR2180721)资助。

摘　　要：克雷伯氏菌在自然界中广泛分布,生长旺盛.其细胞内部除了细胞质外,还具有周质空间和细菌微室等不同微环境,这些区域化的微环境适合一些特殊的代谢途径.这些特点使得克雷伯氏菌成为一类优良的细胞工厂底盘细胞.基因重组或编辑方法是细胞工厂研究的基础,Red重组酶辅助的基因重组系统和基于CRISPR的基因编辑技术已经成功应用于克雷伯氏菌的基因操作.野生型克雷伯氏菌具有合成高水平1,3-丙二醇和2,3-丁二醇等化合物的能力,以这些内源代谢途径为基础,通过代谢工程改造后的工程菌株可以高效生产多种化学品.这些化学品包括:3-羟基丙酸、二羟基丙酮、甘油、1,2-丙二醇、丙醇等甘油代谢途径相关化合物,R-乙偶姻、2-丁酮、仲丁醇等2,3-丁二醇合成途径相关化合物,2-酮基葡萄糖酸、葡萄糖酸、木糖酸等葡萄糖氧化途径相关化合物,以及2-酮基异戊酸、异丁醇、2,3-二羟基异戊酸和缬氨酸等支链氨基酸合成途径相关化合物.这些化合物在生物能源与生物基材料方面具有很好的应用前景.Klebsiella spp.is a group of bacteria that are habited ubiquitously in natural environments.The growth and reproduction of Klebsiella spp.are vigorous and not easily contaminated in culture.Besides the cytoplasm,their cells have the periplasm and microcompartments,which are separated from the cytoplasm and provide special conditions.The glucose oxidization pathway is located in the periplasm,while the 1,2-propanediol catabolism pathway is found in the Pdu microcompartment.Klebsiella spp.are good candidates as chassis for cell factories,and various chemicals have been produced by them.Technologies of gene replacement or gene editing are the bases of cell factory construction.Red recombinase-associated gene replacement and CRISPR-assisted genome editing are powerful tools that have been developed for Klebsiella spp.cell factory construction.Klebsiella spp.are native 1,3-propanediol and 2,3-butanediol producers with high yields and productivities.1,3-Propanediol is a main catabolic product of glycerol metabolism.After expressing of a heterologous aldehyde dehydrogenase,3-hydroxypropionic acid was produced with glycerol as the feedstock.After deletion of the triosephosphate isomerase,1,2-propanediol,and propanol were synthesized from glycerol.After expressing of a Corynebacterium glutamicum dihydroxyacetone phosphate dephosphorylase,dihydroxyacetone and glycerol were produced from glucose.R-acetoin is the precursor of 2,3-butanediol.Disruption of the butanediol dehydrogenase resulted in R-acetoin accumulation in the broth.2,3-Butanediol was further catabolized to 2-butanone and 2-butanol after introducing of a heterologous dehydratase and an alcohol dehydrogenase.2-ketogluconic acid,gluconic acid,and xylonic acid are chemicals that were produced through the glucose oxidation pathway.2,3-Dihydroxyisovalerate,2-ketoisovalerate,and valine are intermediates and the final product of the branched-chain amino acid synthesis pathway and they were accumulated in the culture broth after disrupting the acetolactate decarboxylas

关 键 词：克雷伯氏菌 细胞工厂 生物能源 生物基材料 

分 类 号：Q78[生物学—分子生物学]