Sun Jizhe, Yu Huimin, Chen Jie, Luo Hui, Shen Zhongyao
Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.
Key Laboratory of Industrial Biocatalysis (Tsinghua University), The Ministry of Education, Beijing, 100084, China.
J Ind Microbiol Biotechnol. 2016 Dec;43(12):1631-1639. doi: 10.1007/s10295-016-1840-9. Epub 2016 Oct 19.
Rhodococcus ruber TH was selected as a parent strain to engineer for biomanufacturing of ammonium acrylate; the characteristics of this strain included accelerated growth rate, high cell tolerance and natively overexpressed nitrile hydratase (NHase). Transcriptome analysis revealed that the transcription levels of the native NHase, amidase and nitrilase were extremely high, moderate and extremely low, respectively. Through NHase-amidase double-knockout and amidase single-knockout, the engineered strains R. ruber THdAdN and R. ruber THdA were obtained for overexpression of a heterologous nitrilase from R. rhodochrous tg1-A6 using a urea-induced Pa2 promoter. The nitrilase activity toward substrate acrylonitrile in the engineered THdAdN(Nit) reached 187.0 U/mL at 42 h, threefold of that R. rhodochrous tg1-A6 and 2.3-fold of that of THdA(Nit). The optimal catalysis temperature and pH of the nitrilases in different cells exhibited no significant difference. Using the cells as catalysts, biomanufacturing of ammonium acrylate was performed under room temperature. When catalyzed by the engineered THdAdN(Nit), the titer and productivity of ammonium acrylate dramatically increased to 741.0 g/L and 344.9 g/L/h, which are the highest results reported to date.
红球菌TH被选为用于丙烯酸铵生物制造工程的亲本菌株;该菌株的特点包括生长速率加快、细胞耐受性高以及天然过表达腈水合酶(NHase)。转录组分析表明,天然NHase、酰胺酶和腈水解酶的转录水平分别极高、中等和极低。通过NHase-酰胺酶双敲除和酰胺酶单敲除,利用尿素诱导的Pa2启动子获得了工程菌株红球菌THdAdN和红球菌THdA,用于过表达来自红平红球菌tg1-A6的异源腈水解酶。在42小时时,工程菌株THdAdN(Nit)中腈水解酶对底物丙烯腈的活性达到187.0 U/mL,是红平红球菌tg1-A6的三倍,是THdA(Nit)的2.3倍。不同细胞中腈水解酶的最佳催化温度和pH没有显著差异。以这些细胞为催化剂,在室温下进行丙烯酸铵的生物制造。当由工程菌株THdAdN(Nit)催化时,丙烯酸铵的产量和生产率大幅提高到741.0 g/L和344.9 g/L/h,这是迄今为止报道的最高结果。