Sabido Andrea, Sigala Juan Carlos, Hernández-Chávez Georgina, Flores Noemí, Gosset Guillermo, Bolívar Francisco
Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor., México.
Biotechnol Bioeng. 2014 Jun;111(6):1150-60. doi: 10.1002/bit.25177. Epub 2014 Jan 28.
Phosphoenolpyruvate (PEP) is a precursor involved in the biosynthesis of aromatics and other valuable compounds in Escherichia coli. The PEP:carbohydrate phosphotransferase system (PTS) is the major glucose transport system and the largest PEP consumer. To increase intracellular PEP availability for aromatics production purposes, mutant strains of E. coli JM101 devoid of the ptsHIcrr operon (PB11 strain) have been previously generated. In this derivative, transport and growth rate on glucose decreased significantly. A laboratory evolved strain derived from PB11 that partially recovered its growth capacity on glucose was named PB12. In the present study, we blocked carbon skeletons interchange between PEP and pyruvate (PYR) in these ptsHIcrr(-) strains by deleting the pykA, pykF, and ppsA genes. The PB11 pykAF(-) ppsA(-) strain exhibited no growth on glucose or acetate alone, but it was viable when both substrates were consumed simultaneously. In contrast, the PB12 pykAF(-) ppsA(-) strain displayed a low growth rate on glucose or acetate alone, but in the mixture, growth was significantly improved. RT-qPCR expression analysis of PB11 pykAF(-) ppsA(-) growing with both carbon sources showed a downregulation of all central metabolic pathways compared with its parental PB11 strain. Under the same conditions, transcription of most of the genes in PB12 pykAF(-) ppsA(-) did not change, and few like aceBAK, sfcA, and poxB were overexpressed compared with PB12. We explored the aromatics production capabilities of both ptsHIcrr(-) pykAF(-) ppsA(-) strains and the engineered PB12 pykAF(-) ppsA(-) tyrR(-) pheA(ev2+) /pJLBaroG(fbr) tktA enhanced the yield of aromatic compounds when coutilizing glucose and acetate compared with the control strain PB12 tyrR(-) pheA(ev2+) /pJLBaroG(fbr) tktA.
磷酸烯醇式丙酮酸(PEP)是参与大肠杆菌中芳香族化合物和其他有价值化合物生物合成的前体。PEP:碳水化合物磷酸转移酶系统(PTS)是主要的葡萄糖转运系统,也是最大的PEP消耗者。为了增加用于芳香族化合物生产的细胞内PEP可用性,先前已构建了缺乏ptsHIcrr操纵子的大肠杆菌JM101突变株(PB11菌株)。在这种衍生物中,葡萄糖的转运和生长速率显著降低。从PB11衍生而来的、部分恢复了在葡萄糖上生长能力的实验室进化菌株被命名为PB12。在本研究中,我们通过删除pykA、pykF和ppsA基因,阻断了这些ptsHIcrr(-)菌株中PEP和丙酮酸(PYR)之间的碳骨架交换。PB11 pykAF(-) ppsA(-)菌株单独在葡萄糖或乙酸盐上均无法生长,但当同时消耗这两种底物时能够存活。相比之下,PB12 pykAF(-) ppsA(-)菌株单独在葡萄糖或乙酸盐上生长速率较低,但在混合底物中,生长得到显著改善。对利用两种碳源生长的PB11 pykAF(-) ppsA(-)进行RT-qPCR表达分析表明,与其亲本PB11菌株相比,所有中心代谢途径均下调。在相同条件下,PB12 pykAF(-) ppsA(-)中大多数基因的转录没有变化,与PB12相比,少数基因如aceBAK、sfcA和poxB过表达。我们探究了两种ptsHIcrr(-) pykAF(-) ppsA(-)菌株以及工程化的PB12 pykAF(-) ppsA(-) tyrR(-) pheA(ev2+) /pJLBaroG(fbr) tktA的芳香族化合物生产能力,与对照菌株PB12 tyrR(-) pheA(ev2+) /pJLBaroG(fbr) tktA相比,共利用葡萄糖和乙酸盐时,工程化菌株提高了芳香族化合物的产量。