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首页> 外文期刊>The Internet Journal of Pharmacology >Dissolved Oxygen concentration analysis of L-Lysine Fermentation Production by Corynebacterium glutamicum
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Dissolved Oxygen concentration analysis of L-Lysine Fermentation Production by Corynebacterium glutamicum

机译：谷氨酸棒杆菌发酵生产L-赖氨酸的溶解氧浓度分析

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The L-lysine fermentation by Corneybacterium glutamicium was investigated in this study. The objective was to improve the process performance by manipulating cellular environment conditions. The main factor under consideration was dissolved oxygen concentrations in the fermentation broth. To implement effective process control, a process model was developed based on combined kinetic study and material balances. The process dynamics at the dissolved oxygen tensions (DOTs) of 5%, 10% and 20% was analyzed. The results showed that inhibition of high oxygen level could occur during the early growth phase and depressive effect of low oxygen availability was confined to the rest of the process, suggesting that different fermentation stages required different DOTs. Batch experiments were conducted with 5% DOT for the rest of fermentation. The final L-Lysine concentration reached 52.7g/L compared with 40g/L The low DOT settings required much less energy for agitation and aeration. Introduction Out of the twenty naturally occurring amino acids, L -lysine (C6H14N2O2; MW 146.19) is the one of the nine essential amino acid. It's major commercially form is L-lysine –HCL (L - lysine monohydrochloride (Liebl et al., 1991). L- Lysine is commonly produced in a stable and non-hygroscopic hydro chlorinated form of purity higher than 98.5% and moisture content less than 1% (Fechter et al., 1997). It is mainly used as a feed additive in the animal feed industry, mixed with various common live stock such as cereals which do not contain sufficient levels of L-lysine for the live stock's nutritional requirement especially for single stomach animals like broilers, poultry, and swine (Zelder, et al., 2005). (Ishii et al., 1997), and as supplement for humans, improving the feed quality by increasing the absorption of other amino acids. (Georgen et al., 1982). As a fine chemical it is used in human medicine, in cosmetics and in the pharmaceutical industry, particularly as ingredients of infusion solution for pharmaceutical application (Zelder et al., 2005) and as precursor for industrial chemicals. Further more, a production method for industrially producing an optically active lysine derivative useful as a pharmaceutical intermediate is described in Nakazawa et al., 2006. Several hundred thousand tones of L- lysine (800,000 tones/year) are presumably produced annually world wide, almost exclusively using bacterial fermentations. US6984512and WO2005/059139 (Zelder et al., 2005), (Liaw et al., 2006) refer to an annual L-lysine production of approximately 250,000tonnes, instead. Optimal oxygen transfer is perhaps the most difficult task to accomplish. Oxygen is poorly soluble in water -and even less in fermentation broths- and is relatively scarce in air (20.8%). Oxygen transfer is usually helped by agitation, which is also needed to mix nutrients and to keep the fermentation homogeneous. There is however limits to the speed of agitation, due both to high power consumption (that's proportional to the cube of the speed) and the damage to organisms due to excessive tip speed. No significant information has been found in patent literature regarding the effect of air saturation and a little is known regarding the real effect of oxygen on L-lysine fermentation. L-lysine fermentation is an aerobic process [Shimazaki et al., 1983, Tosaka et al., 1981, Asakura etal. 1999] demanding large amounts of oxygen and strongly influenced by the air saturation in bioreactor. Lactic acid is formed as a byproduct under anaerobic conditions, which is reconsumed after the establishment of aerobic conditions. Aerobic conditions are maintained by aseptically adding to the culture oxygen containing gaseous mixtures, e.g. atmospheric air or pure oxygen [Kreutzer et al., 2001, Bathe et al., 2004]. Cultivation of L-lysine producing microorganisms is carried out with shaking of shake flasks (250-300 rpm) or by the aeration (0.5-1.5 vvm) of stirring bioreactors. US5268293 and US6984512
机译：本研究研究了谷氨酸棒杆菌发酵L-赖氨酸的过程。目的是通过操纵蜂窝环境条件来改善过程性能。考虑的主要因素是发酵液中的溶解氧浓度。为了实施有效的过程控制，在动力学研究和物料平衡相结合的基础上开发了过程模型。分析了溶解氧张力（DOT）为5％，10％和20％时的过程动力学。结果表明，高氧水平的抑制作用可能发生在生长的早期，而低氧可利用性的抑制作用仅限于其余过程，这表明不同的发酵阶段需要不同的DOT。对于其余的发酵，使用5％DOT进行批次实验。最终的L-赖氨酸浓度达到40,7 g / L时达到52.7 g / L。低DOT设置所需的搅拌和充气能量要少得多。简介在20种天然氨基酸中，L-赖氨酸（C6H14N2O2; MW 146.19）是9种必需氨基酸之一。它的主要商业形式是L-赖氨酸-HCL（L-赖氨酸一盐酸盐（Liebl等，1991）。L-赖氨酸通常以稳定且非吸湿性的氯化形式生产，纯度高于98.5％，水分含量少含量不到1％（Fechter et al。，1997）。它在动物饲料工业中主要用作饲料添加剂，与各种常见的牲畜混合在一起，例如谷物，其中L-赖氨酸含量不足以补充牲畜的营养尤其是对于单胃动物（如肉鸡，家禽和猪）的需求（Zelder等，2005）（Ishii等，1997），作为人类的补充，通过增加其他氨基酸的吸收来改善饲料质量（Georgen et al。，1982）。作为一种精细化学品，它被用于人类医学，化妆品和制药行业，尤其​​是用作制药用输液溶液的成分（Zelder et al。，2005）和前体。工业化学品。此外，生产Nakazawa et al。，2006中描述了工业生产用作药物中间体的光学活性赖氨酸衍生物的方法。据估计，全世界每年大约生产数十万吨的L-赖氨酸（800,000吨/年），几乎全部使用细菌发酵。 US6984512和WO2005 / 059139（Zelder等人，2005）（Liaw等人，2006）是指每年约25万吨的L-赖氨酸生产。最佳的氧气传输可能是最难完成的任务。氧气在水中的溶解度很差-在发酵液中甚至更少-并且空气中相对稀缺（20​​.8％）。氧气转移通常是通过搅拌来帮助的，这也是混合营养和保持发酵均匀的必要条件。但是，由于高功率消耗（与速度的立方成正比）和过度的叶尖速度对生物的破坏，搅拌速度受到限制。在专利文献中没有发现关于空气饱和的影响的重要信息，而关于氧气对L-赖氨酸发酵的实际影响的知之甚少。 L-赖氨酸发酵是有氧过程[Shimazaki等，1983; Tosaka等，1981;朝仓等。 [1999]要求大量的氧气，并受到生物反应器中空气饱和度的强烈影响。乳酸在厌氧条件下作为副产物形成，需氧条件建立后会重新消耗。通过向培养物中无菌地添加含氧的气体混合物，例如氧气，来维持有氧条件。大气或纯氧[Kreutzer等，2001; Bathe等，2004]。培养L-赖氨酸的微生物的培养通过摇瓶摇动（250-300rpm）或通过搅拌生物反应器的通气（0.5-1.5vvm）来进行。 US5268293和US6984512

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