Xu Yun-Zhen, Guo Ni-Ni, Zheng Zong-Ming, Ou Xian-Jin, Liu Hong-Juan, Liu De-Hua
Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
Biotechnol Bioeng. 2009 Dec 1;104(5):965-72. doi: 10.1002/bit.22455.
Klebsiella pneumoniae HR526, a new isolated 1,3-propanediol (1,3-PD) producer, exhibited great productivity. However, the accumulation of lactate in the late-exponential phase remained an obstacle of 1,3-PD industrial scale production. Hereby, mutants lacking D-lactate pathway were constructed by knocking out the ldhA gene encoding fermentative D-lactate dehydrogenase (LDH) of HR526. The mutant K. pneumoniae LDH526 with the lowest LDH activity was studied in aerobic fed-batch fermentation. In experiments using pure glycerol as feedstock, the 1,3-PD concentrations, conversion, and productivity increased from 95.39 g L(-1), 0.48 and 1.98 g L(-1) h(-1) to 102. 06 g L(-1), 0.52 mol mol(-1) and 2.13 g L(-1) h(-1), respectively. The diol (1,3-PD and 2,3-butanediol) conversion increased from 0.55 mol mol(-1) to a maximum of 0.65 mol mol(-1). Lactate would not accumulate until 1,3-PD exceeded 84 g L(-1), and the final lactate concentration decreased dramatically from more than 40 g L(-1) to <3 g L(-1). Enzymic measurements showed LDH activity decreased by 89-98% during fed-batch fermentation, and other related enzyme activities were not affected. NADH/NAD(+) enhanced more than 50% in the late-exponential phase as the D-lactate pathway was cut off, which might be the main reason for the change of final metabolites concentrations. The ability to utilize crude glycerol from biodiesel process and great genetic stability demonstrated that K. pnemoniae LDH526 was valuable for 1,3-PD industrial production.
肺炎克雷伯菌HR526是一种新分离出的1,3 - 丙二醇(1,3 - PD)生产菌,具有很高的生产能力。然而,在指数生长后期乳酸的积累仍然是1,3 - PD工业规模生产的一个障碍。因此,通过敲除编码HR526发酵型D - 乳酸脱氢酶(LDH)的ldhA基因构建了缺乏D - 乳酸途径的突变体。对LDH活性最低的突变体肺炎克雷伯菌LDH526进行了好氧补料分批发酵研究。在以纯甘油为原料的实验中,1,3 - PD浓度、转化率和生产率分别从95.39 g L⁻¹、0.48和1.98 g L⁻¹ h⁻¹增加到102.06 g L⁻¹、0.52 mol mol⁻¹和2.13 g L⁻¹ h⁻¹。二醇(1,3 - PD和2,3 - 丁二醇)转化率从0.55 mol mol⁻¹增加到最大0.65 mol mol⁻¹。直到1,3 - PD超过84 g L⁻¹乳酸才会积累,最终乳酸浓度从超过40 g L⁻¹急剧下降到<3 g L⁻¹。酶活性测定表明,在补料分批发酵过程中LDH活性下降了89 - 98%,而其他相关酶活性未受影响。由于D - 乳酸途径被切断,在指数生长后期NADH/NAD⁺增加了50%以上,这可能是最终代谢物浓度变化的主要原因。利用生物柴油过程中粗甘油的能力以及良好的遗传稳定性表明肺炎克雷伯菌LDH526对1,3 - PD的工业生产具有重要价值。