Institute of Bio- and Geosciences, IBG-1: Biotechnology, Systems Biotechnology, Forschungszentrum Jülich, Jülich 52425, Germany.
Biotechnol Bioeng. 2013 Jan;110(1):220-8. doi: 10.1002/bit.24616. Epub 2012 Aug 13.
Fast growth of industrial microorganisms, such as Corynebacterium glutamicum, is a direct amplifier for the productivity of any growth coupled or decoupled production process. Recently, it has been shown that C. glutamicum when grown in a novel picoliter bioreactor (PLBR) exhibits a 50% higher growth rate compared to a 1 L batch cultivation [Grünberger et al. (2012) Lab Chip]. We here compare growth of C. glutamicum with glucose as substrate at different scales covering batch cultivations in the liter range down to single cell cultivations in the picoliter range. The maximum growth rate of standard batch cultures as estimated from different biomass quantification methods is mu = 0.42 ± 0.03 h(-1) even for microtiter scale cultivations. In contrast, growth in a microfluidic perfusion system enabling analysis of single cells reproducibly reveals a higher growth rate of mu = 0.62 ± 0.02 h(-1). When in the same perfusion system cell-free supernatant from exponentially grown shake flask cultures is used the growth rate of single cells is reduced to mu = 0.47 ± 0.02 h(-1). Likewise, when fresh medium is additionally supplied with 5 mM acetate, a growth rate of mu = 0.51 ± 0.01 h(-1) is determined. These results prove that higher growth rates of C. glutamicum than known from typical batch cultivations are possible, and that growth is definitely impaired by very low concentrations of byproducts such as acetate.
工业微生物（如谷氨酸棒杆菌）的快速生长是任何与生长偶联或不偶联的生产过程生产力的直接放大。最近，已经表明，当在新型皮升生物反应器（PLBR）中生长时，与 1 L 分批培养相比，谷氨酸棒杆菌的生长速度提高了 50％[Grünberger 等人，（2012）Lab Chip]。在这里，我们比较了以葡萄糖为底物的谷氨酸棒杆菌在不同规模下的生长情况，涵盖了从 1 升规模的分批培养到皮升规模的单细胞培养。通过不同的生物量定量方法估计的标准分批培养的最大生长速率为 mu = 0.42 ± 0.03 h(-1)，即使是在微量培养规模下。相比之下，在微流控灌注系统中，能够可重复地分析单细胞的生长，显示出更高的生长速率 mu = 0.62 ± 0.02 h(-1)。当在相同的灌注系统中使用指数生长期摇瓶培养的无细胞上清液时，单细胞的生长速率降低到 mu = 0.47 ± 0.02 h(-1)。同样，当新鲜培养基中另外添加 5 mM 乙酸盐时，确定的生长速率为 mu = 0.51 ± 0.01 h(-1)。这些结果证明，谷氨酸棒杆菌的生长速度比典型的分批培养中已知的要高，并且生长确实受到低浓度副产物（如乙酸盐）的严重影响。
