CN111893145A - A new method for intelligent biological fermentation of lysine - Google Patents

A new method for intelligent biological fermentation of lysine Download PDF

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CN111893145A
CN111893145A CN202010815128.9A CN202010815128A CN111893145A CN 111893145 A CN111893145 A CN 111893145A CN 202010815128 A CN202010815128 A CN 202010815128A CN 111893145 A CN111893145 A CN 111893145A
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tail gas
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高世军
王志强
吴泽华
徐文昌
李刚
张�杰
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Linqing Deneng Goldencorn Biological Co ltd
Shouguang Jinyuandong Denatured Starch Co ltd
Shouguang Jinyumi Biotechnology Co ltd
SHANDONG SHOUGUANG JUNENG GROUP GOLDEN CORN CO LTD
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Linqing Deneng Goldencorn Biological Co ltd
Shouguang Jinyuandong Denatured Starch Co ltd
Shouguang Jinyumi Biotechnology Co ltd
SHANDONG SHOUGUANG JUNENG GROUP GOLDEN CORN CO LTD
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Abstract

本发明提供一种赖氨酸智能生物发酵新方法,涉及生物发酵技术领域。该赖氨酸智能生物发酵新方法,包括以下步骤:1)菌体生物量与产酸浓度、碳源流加量、氮源流加量关联:S1、菌体菌体量的在线检测使用微生物浓度在线分析仪进行检测,实时的获取发酵罐中微生物的浓度;S2、通过对上述获取的大批试验数据进行理论分析,对于不同时期的菌体生物量、产酸浓度、碳源流加量、氮源流加量进行分析。本发明,将发酵过程中的各项参数进行整合关联,将菌体量与产酸速率、碳源、氮源消耗速率,尾气分析数据与溶氧控制进行关联,实现发酵过程的自动控制、自动流加,最大限度的减少人工操作,实现智能化发酵。The invention provides a new method for intelligent biological fermentation of lysine, which relates to the technical field of biological fermentation. The new method for intelligent biological fermentation of lysine includes the following steps: 1) Correlation between bacterial biomass and acid production concentration, carbon source flow addition, and nitrogen source flow addition: S1, the online detection of the bacterial cell amount uses the online concentration of microorganisms The analyzer detects and obtains the concentration of microorganisms in the fermentor in real time; S2, through theoretical analysis of the above-obtained large quantities of test data, the bacterial biomass, acid production concentration, carbon source flow addition, and nitrogen source flow addition in different periods are analyzed. quantity is analyzed. The invention integrates and correlates various parameters in the fermentation process, correlates the amount of bacteria with the acid production rate, carbon source, nitrogen source consumption rate, and tail gas analysis data and dissolved oxygen control, so as to realize automatic control and automatic control of the fermentation process. Flow addition minimizes manual operations and realizes intelligent fermentation.

Description

一种赖氨酸智能生物发酵新方法A new method for intelligent biological fermentation of lysine

技术领域technical field

本发明涉及生物发酵技术领域,具体为一种赖氨酸智能生物发酵新方法。The invention relates to the technical field of biological fermentation, in particular to a new method for intelligent biological fermentation of lysine.

背景技术Background technique

发酵罐是一种生物反应器,生物反应器是指为活细胞或酶提供适宜的反应环境,让它们进行细胞增殖或生产的装置系统。生物反应器为细菌的生长和繁殖提供适宜的生长环境,促进菌体生产人们需要的产物。A fermenter is a bioreactor, and a bioreactor refers to a device system that provides a suitable reaction environment for living cells or enzymes to allow them to proliferate or produce. The bioreactor provides a suitable growth environment for the growth and reproduction of bacteria, and promotes the bacteria to produce the products people need.

目前,国内发酵罐的制作都不存在较大的差距,但控制系统差别很大,单片机类的DCS群控系统成本低,但操作系统较为繁琐,运行质量不佳,维修费用高。基于PLC集成模块可编程控制系统及相应的总线控制技术,运行质量稳定,维修费用低,可智能化编程,实现自动控制。At present, there is no big gap in the production of domestic fermentation tanks, but the control systems are very different. The DCS group control system of the single chip type has low cost, but the operating system is relatively cumbersome, the operation quality is not good, and the maintenance cost is high. Based on the PLC integrated module programmable control system and the corresponding bus control technology, the operation quality is stable, the maintenance cost is low, and it can be programmed intelligently to realize automatic control.

目前我们对赖氨酸发酵的研究已进入瓶颈期,我们的研究多集中于发酵过程的某一方面,而发酵是一种复杂的生化过程,影响发酵过程的因素较多,从宏观水平的培养基配比、发酵温度、原料质量等到微观水平的微生物次级代谢、代谢调控等,都会对发酵过程产生不可逆的影响。发酵过程和化工过程最主要的区别就在于发酵过程有活体的微生物细胞参与进行,相对于整个发酵系统,微生物代谢是一个开放的系统,需要不断与周围环境发生物质交换、能量交换来维持细胞的生命活动,生命行为的复杂性使发酵过程比化学催化过程更加难控制,因此外部环境对微生物的胞内代谢的影响和目标代谢物的合成具有重要作用。At present, our research on lysine fermentation has entered a bottleneck period. Our research mostly focuses on one aspect of the fermentation process. Fermentation is a complex biochemical process, and there are many factors affecting the fermentation process. The base ratio, fermentation temperature, raw material quality, etc. to the micro-level microbial secondary metabolism, metabolic regulation, etc., will have an irreversible impact on the fermentation process. The main difference between the fermentation process and the chemical process is that the fermentation process involves the participation of living microbial cells. Compared with the entire fermentation system, microbial metabolism is an open system, which requires constant exchange of substances and energy with the surrounding environment to maintain the cell's metabolism. The complexity of life activities and behaviors makes the fermentation process more difficult to control than the chemical catalysis process. Therefore, the influence of the external environment on the intracellular metabolism of microorganisms and the synthesis of target metabolites plays an important role.

发酵工业在产品研发、新设备和新技术的应用上一直更新不断,要实现发酵过程的化化与控制,必须要解决好以下问题:首先是生物模型的建立:其次是传感器技术的应用;第三是复杂生物过程的优化技术;第四发酵过程的系统动力学;最后还要通过接口技术在发酵系统和检测系统间建立合适链接。次级代谢产物的产生过程较为复杂,高产菌株表现出高产性状需要分子水平的遗传特性、细胞水平的代谢特性和工程水平的传质特性三个水平同时发生相互作用,只要某一水平环节上产生瓶颈就会产生全局性影响。因此通过各类筛选手段获得的高产菌株,要在生产上表现高产性状,还需要结合基础理论研究,经过大量试验的推理、验证,运用各类现代化检测手段,获得多种在线的直接参数、间接参数以及离线参数,通过多尺度的相关性分析建立菌株的生理特性和生物合成过程的关联,从而有针对性的提高赖氨酸生产菌的产量,并指导高产菌株的选育工作。The fermentation industry has been constantly updated in product research and development, application of new equipment and new technologies. To realize the chemicalization and control of the fermentation process, the following problems must be solved: first, the establishment of biological models; second, the application of sensor technology; third The third is the optimization technology of the complex biological process; the fourth is the system dynamics of the fermentation process; finally, the appropriate link between the fermentation system and the detection system must be established through the interface technology. The production process of secondary metabolites is relatively complex, and high-yielding strains exhibit high-yield traits that require the simultaneous interaction of three levels: genetic characteristics at the molecular level, metabolic characteristics at the cellular level, and mass transfer characteristics at the engineering level. Bottlenecks have global impacts. Therefore, the high-yielding strains obtained through various screening methods need to combine basic theoretical research, and use various modern detection methods to obtain a variety of online direct parameters, indirect parameters, and indirect parameters. Parameters and offline parameters, through multi-scale correlation analysis, establish the correlation between the physiological characteristics of the strain and the biosynthetic process, so as to improve the yield of lysine-producing bacteria and guide the selection of high-yielding strains.

基于上述原因,我们认识到,在生物医药、食品等工业发酵过程中,尾气氧及尾气二氧化碳的测定对了解发酵过程的宏观生理代谢特性非常重要。通过对尾气氧和二氧化碳的测定,可在线计算出细胞重要生理代谢特征参数氧消耗速率(OUR)、二氧化碳生产速率(CER)和呼吸商(RQ),进而实现对发酵过程的有效调控。在线质谱仪测量精度高、漂移小,可以同时测量多种发酵尾气组分,响应快且可多罐尾气循环连续测量,是提供发酵尾气实时信息的理想工具。Based on the above reasons, we realize that in the industrial fermentation process of biomedicine and food, the determination of tail gas oxygen and tail gas carbon dioxide is very important to understand the macroscopic physiological and metabolic characteristics of the fermentation process. The oxygen consumption rate (OUR), carbon dioxide production rate (CER) and respiration quotient (RQ) can be calculated online by measuring the oxygen and carbon dioxide in the exhaust gas, which can effectively control the fermentation process. The online mass spectrometer has high measurement accuracy and small drift. It can measure a variety of fermentation exhaust gas components at the same time, with fast response and continuous measurement of multi-tank exhaust gas circulation. It is an ideal tool to provide real-time information of fermentation exhaust gas.

目前,现有技术中发酵系统的控制已经实现了自动灭菌和自动配料,减少了人员的操作,但补料-分批发酵过程中的补料操作还离不开人工经验的操作,需要控制不同时期的碳源流加量和氮源及生长因子的流加量,在满足菌体生长产酸的基础上避免过量积累,对菌体活力产生影响,同时,对于好氧发酵来说,发酵过程中的溶氧控制仍需要人工进行调整风量和搅拌,目前的发酵控制系统需要人工操作较多,智能化程度不够。At present, the control of the fermentation system in the prior art has achieved automatic sterilization and automatic batching, which reduces the operation of personnel. However, the feeding operation in the feeding-batch fermentation process is inseparable from the operation of manual experience, and it is necessary to control The flow rate of carbon source and nitrogen source and growth factor in different periods can avoid excessive accumulation on the basis of satisfying the growth and acid production of the bacteria, and have an impact on the vitality of the bacteria. At the same time, for aerobic fermentation, the fermentation process The dissolved oxygen control in the fermentation still requires manual adjustment of air volume and stirring. The current fermentation control system requires more manual operations, and the degree of intelligence is not enough.

发明内容SUMMARY OF THE INVENTION

(一)解决的技术问题(1) Technical problems solved

针对现有技术的不足,本发明提供了一种赖氨酸智能生物发酵新方法,解决了现有技术中存在的缺陷与不足。Aiming at the deficiencies of the prior art, the present invention provides a new method for intelligent biological fermentation of lysine, which solves the defects and deficiencies in the prior art.

(二)技术方案(2) Technical solutions

为实现以上目的,本发明通过以下技术方案予以实现:一种赖氨酸智能生物发酵新方法,所述工艺包括以下步骤:In order to achieve the above purpose, the present invention is achieved through the following technical solutions: a new method for intelligent biological fermentation of lysine, the process comprises the following steps:

1)菌体生物量与产酸浓度、碳源流加量、氮源流加量关联:1) Bacterial biomass is related to acid production concentration, carbon source flow addition, and nitrogen source flow addition:

S1、菌体菌体量的在线检测使用微生物浓度在线分析仪进行检测,实时的获取发酵罐中微生物的浓度,将获取的数值依次标记为W1、W2、W3...WnS1. The on-line detection of the amount of bacteria is carried out by using a microorganism concentration online analyzer to obtain the concentration of microorganisms in the fermentor in real time, and the obtained values are sequentially marked as W 1 , W 2 , W 3 . . . W n ;

S2、通过对上述获取的大批试验数据进行理论分析,对于不同时期的菌体生物量、产酸浓度、碳源流加量、氮源流加量进行分析,依次获取菌体生物量U、产酸浓度K、碳源流加量C、氮源流加量V;S2. Through theoretical analysis of a large number of experimental data obtained above, analyze the bacterial biomass, acid production concentration, carbon source flow addition, and nitrogen source flow addition in different periods, and sequentially obtain the bacterial biomass U and acid production concentration. K, carbon source flow addition C, nitrogen source flow addition V;

S3、根据上述分析,将菌体生物量与产酸浓度、碳源流加量、氮源流加量关联,对不同发酵时期确定不同的控制标准;S3. According to the above analysis, correlate the bacterial biomass with the acid production concentration, the carbon source flow addition, and the nitrogen source flow addition, and determine different control standards for different fermentation periods;

2)尾气数据与溶氧控制关联:2) The tail gas data is related to dissolved oxygen control:

S1、结合在线尾气分析仪,对发酵尾气中氧气含量及二氧化碳含量进行分析,得到分析结果,标记氧气含量为L1,二氧化碳含量L2S1. Combine the on-line tail gas analyzer to analyze the oxygen content and carbon dioxide content in the fermentation tail gas, and obtain the analysis result, marking the oxygen content as L 1 and the carbon dioxide content as L 2 ;

S2、根据氧气含量及二氧化碳含量分析结果,得出赖氨酸发酵氧消耗速率和二氧化碳生产速率及呼吸商,通过尾气中氧气和二氧化碳的含量直接反映出赖氨酸代谢过程的变化情况;S2. According to the analysis results of oxygen content and carbon dioxide content, the oxygen consumption rate, carbon dioxide production rate and respiration quotient of lysine fermentation are obtained, and the changes of lysine metabolic process are directly reflected by the content of oxygen and carbon dioxide in the exhaust gas;

S3、通过改变不同的发酵条件,控制其中一个变量,分析尾气的变化情况,结合发酵过程指标的变化,得出发酵条件对赖氨酸发酵产量及转化率的影响结果;S3. By changing different fermentation conditions, controlling one of the variables, analyzing the change of tail gas, and combining the changes of fermentation process indicators, the effect of fermentation conditions on lysine fermentation yield and conversion rate is obtained;

S4、根据上述结果,将尾气数据与溶氧控制关联,对发酵控制条件进行相应的调整。S4. According to the above results, correlate the exhaust gas data with the dissolved oxygen control, and adjust the fermentation control conditions accordingly.

优选的,所述菌体生物量与产酸浓度、碳源流加量、氮源流加量关联中,还包括以下内容:Preferably, in the correlation between the bacterial biomass and the acid production concentration, the carbon source flow addition, and the nitrogen source flow addition, the following contents are also included:

i)以底糖消耗完溶氧上升为控制起点,此时菌体处于对数生长期,菌体量上升较快,糖消耗上升,产酸速率增加,而菌体进入稳定期后,糖消耗稳定,产酸速率稳定,之后进入发酵后期,碳源消耗下降,产酸速率下降;i) Take the bottom sugar consumption and dissolved oxygen rise as the control starting point. At this time, the bacterial cells are in the logarithmic growth phase, the bacterial mass increases rapidly, the sugar consumption increases, and the acid production rate increases, and after the bacterial cells enter the stable phase, the sugar consumption Stable, the acid production rate is stable, and then in the late stage of fermentation, the carbon source consumption decreases, and the acid production rate decreases;

ii)通过实验分析,建立不同阶段的流加公式,按照前期人工流加的控制经验,通过计算得出不同发酵时期的流加系数,实现菌体生物量与碳源流加量的自动关联,计算公式如下:ii) Through experimental analysis, establish the feeding formula of different stages, according to the control experience of artificial feeding in the early stage, obtain the feeding coefficient of different fermentation periods by calculation, realize the automatic correlation between bacterial biomass and carbon source feeding, calculate The formula is as follows:

a=c*v+d+p;a=c*v+d+p;

式中,a为糖流加速率(t/m3·h);In the formula, a is the sugar flow acceleration rate (t/m 3 ·h);

c为常数;c is a constant;

v为单位菌体增量(g/m3·h);v is the unit cell increment (g/m 3 ·h);

d为糖消耗速率(t/m3·h);d is the sugar consumption rate (t/m 3 ·h);

p为残糖控制(5g/L);p is residual sugar control (5g/L);

iii)氮源流加量根据不同时期的氮源消耗水平与碳源流加量进行关联,按照前期试验得出不同时期的碳/氮比,实现氮源流加量与碳源流加量的自动关联;iii) The nitrogen source flow addition amount is correlated with the carbon source flow addition amount according to the nitrogen source consumption level in different periods, and the carbon/nitrogen ratio in different periods is obtained according to the previous test, so as to realize the automatic correlation between the nitrogen source flow addition amount and the carbon source flow addition amount;

iv)按照上述计算出的流加系数,在控制系统中将各参数进行关联,实现菌体生物量与碳源流加量、氮源流加量关联,实现自动控制。iv) Correlate each parameter in the control system according to the flow addition coefficient calculated above to realize the correlation between the bacterial biomass and the carbon source flow addition and the nitrogen source flow addition, and realize automatic control.

优选的,所述尾气数据与溶氧控制关联中,还包括以下内容:Preferably, the correlation between the exhaust gas data and the dissolved oxygen control further includes the following content:

i)通过前期试验确定最低溶氧界限为25%,发酵系统中设置最低溶氧控制值为25%;i) The minimum dissolved oxygen limit is determined to be 25% through the preliminary test, and the minimum dissolved oxygen control value is set to 25% in the fermentation system;

ii)以尾气分析数据确定风量与搅拌的协调关系,通过分析尾气数据及发酵过程指标,确定先提风量还是先调转速,分析发酵成本,并通过实验数据反映调节方式的影响,以不影响发酵转化率为基础,确定最优的调整方案;ii) Determine the coordination relationship between the air volume and stirring based on the exhaust gas analysis data. By analyzing the exhaust gas data and fermentation process indicators, determine whether to increase the air volume first or adjust the rotation speed first, analyze the fermentation cost, and reflect the influence of the adjustment method through the experimental data, so as not to affect the fermentation Based on the conversion rate, determine the optimal adjustment plan;

iii)更进一步的通过分析尾气数据,控制合适的氧气浓度和二氧化碳浓度,将风量与消耗连锁,根据糖流加速度调整风量供应。iii) Further, by analyzing the exhaust gas data, control the appropriate oxygen concentration and carbon dioxide concentration, link the air volume and consumption, and adjust the air volume supply according to the acceleration of sugar flow.

(三)有益效果(3) Beneficial effects

本发明提供了一种赖氨酸智能生物发酵新方法。具备以下有益效果:The invention provides a new method for intelligent biological fermentation of lysine. Has the following beneficial effects:

本发明,将发酵过程中的各项参数进行整合关联,将菌体量与产酸速率、碳源、氮源消耗速率,尾气分析数据与溶氧控制进行关联,实现发酵过程的自动控制、自动流加,最大限度的减少人工操作,实现智能化发酵。The invention integrates and correlates various parameters in the fermentation process, correlates the amount of bacteria with the acid production rate, carbon source, nitrogen source consumption rate, and tail gas analysis data and dissolved oxygen control, so as to realize automatic control and automatic control of the fermentation process. Flow addition minimizes manual operations and realizes intelligent fermentation.

具体实施方式Detailed ways

下面将结合本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。The following will clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

实施例:Example:

本发明实施例提供一种赖氨酸智能生物发酵新方法,该工艺包括以下步骤:The embodiment of the present invention provides a new method for intelligent biological fermentation of lysine, which comprises the following steps:

1)菌体生物量与产酸浓度、碳源流加量、氮源流加量关联:1) Bacterial biomass is related to acid production concentration, carbon source flow addition, and nitrogen source flow addition:

S1、菌体菌体量的在线检测使用微生物浓度在线分析仪进行检测,实时的获取发酵罐中微生物的浓度,将获取的数值依次标记为W1、W2、W3...WnS1. The on-line detection of the amount of bacteria is carried out by using a microorganism concentration online analyzer to obtain the concentration of microorganisms in the fermentor in real time, and the obtained values are sequentially marked as W 1 , W 2 , W 3 . . . W n ;

S2、通过对上述获取的大批试验数据进行理论分析,对于不同时期的菌体生物量、产酸浓度、碳源流加量、氮源流加量进行分析,依次获取菌体生物量U、产酸浓度K、碳源流加量C、氮源流加量V;S2. Through theoretical analysis of a large number of experimental data obtained above, analyze the bacterial biomass, acid production concentration, carbon source flow addition, and nitrogen source flow addition in different periods, and sequentially obtain the bacterial biomass U and acid production concentration. K, carbon source flow addition C, nitrogen source flow addition V;

S3、根据上述分析,将菌体生物量与产酸浓度、碳源流加量、氮源流加量关联,对不同发酵时期确定不同的控制标准;S3. According to the above analysis, correlate the bacterial biomass with the acid production concentration, the carbon source flow addition, and the nitrogen source flow addition, and determine different control standards for different fermentation periods;

本发明中,菌体生物量与产酸浓度、碳源流加量、氮源流加量关联中,还包括以下内容:In the present invention, the correlation between bacterial biomass and acid production concentration, carbon source flow addition, and nitrogen source flow addition also includes the following content:

i)以底糖消耗完溶氧上升为控制起点,此时菌体处于对数生长期,菌体量上升较快,糖消耗上升,产酸速率增加,而菌体进入稳定期后,糖消耗稳定,产酸速率稳定,之后进入发酵后期,碳源消耗下降,产酸速率下降;i) Take the bottom sugar consumption and dissolved oxygen rise as the control starting point. At this time, the bacterial cells are in the logarithmic growth phase, the bacterial mass increases rapidly, the sugar consumption increases, and the acid production rate increases, and after the bacterial cells enter the stable phase, the sugar consumption Stable, the acid production rate is stable, and then in the late stage of fermentation, the carbon source consumption decreases, and the acid production rate decreases;

ii)通过实验分析,建立不同阶段的流加公式,按照前期人工流加的控制经验,通过计算得出不同发酵时期的流加系数,实现菌体生物量与碳源流加量的自动关联,计算公式如下:ii) Through experimental analysis, establish the feeding formula of different stages, according to the control experience of artificial feeding in the early stage, obtain the feeding coefficient of different fermentation periods by calculation, realize the automatic correlation between bacterial biomass and carbon source feeding, calculate The formula is as follows:

a=c*v+d+p;a=c*v+d+p;

式中,a为糖流加速率(t/m3·h);In the formula, a is the sugar flow acceleration rate (t/m 3 ·h);

c为常数;c is a constant;

v为单位菌体增量(g/m3·h);v is the unit cell increment (g/m 3 ·h);

d为糖消耗速率(t/m3·h);d is the sugar consumption rate (t/m 3 ·h);

p为残糖控制(5g/L);p is residual sugar control (5g/L);

iii)氮源流加量根据不同时期的氮源消耗水平与碳源流加量进行关联,按照前期试验得出不同时期的碳/氮比,实现氮源流加量与碳源流加量的自动关联;iii) The nitrogen source flow addition amount is correlated with the carbon source flow addition amount according to the nitrogen source consumption level in different periods, and the carbon/nitrogen ratio in different periods is obtained according to the previous test, so as to realize the automatic correlation between the nitrogen source flow addition amount and the carbon source flow addition amount;

iv)按照上述计算出的流加系数,在控制系统中将各参数进行关联,实现菌体生物量与碳源流加量、氮源流加量关联,实现自动控制;iv) According to the above-mentioned calculated flow addition coefficient, each parameter is correlated in the control system, so as to realize the correlation between the bacterial biomass and the carbon source flow addition and the nitrogen source flow addition, and realize automatic control;

2)尾气数据与溶氧控制关联:2) The tail gas data is related to dissolved oxygen control:

S1、结合在线尾气分析仪,对发酵尾气中氧气含量及二氧化碳含量进行分析,得到分析结果,标记氧气含量为L1,二氧化碳含量L2S1. Combine the on-line tail gas analyzer to analyze the oxygen content and carbon dioxide content in the fermentation tail gas, and obtain the analysis result, marking the oxygen content as L 1 and the carbon dioxide content as L 2 ;

S2、根据氧气含量及二氧化碳含量分析结果,得出赖氨酸发酵氧消耗速率和二氧化碳生产速率及呼吸商,通过尾气中氧气和二氧化碳的含量直接反映出赖氨酸代谢过程的变化情况,对了解赖氨酸发酵过程中控制参数的变化对代谢过程的影响有直观的体现;S2. According to the analysis results of oxygen content and carbon dioxide content, the oxygen consumption rate, carbon dioxide production rate and respiration quotient of lysine fermentation are obtained. The changes of control parameters in the lysine fermentation process have an intuitive reflection on the metabolic process;

S3、通过改变不同的发酵条件,控制其中一个变量,分析尾气的变化情况,结合发酵过程指标的变化,得出发酵条件对赖氨酸发酵产量及转化率的影响结果;S3. By changing different fermentation conditions, controlling one of the variables, analyzing the change of tail gas, and combining the changes of fermentation process indicators, the effect of fermentation conditions on lysine fermentation yield and conversion rate is obtained;

S4、根据上述结果,将尾气数据与溶氧控制关联,对发酵控制条件进行相应的调整,更精细化控制工艺,使得赖氨酸生产转化率能够进一步提高,提高产量,节省发酵成本;S4. According to the above results, the tail gas data is correlated with the dissolved oxygen control, and the fermentation control conditions are adjusted accordingly, and the control process is more refined, so that the lysine production conversion rate can be further improved, the yield is increased, and the fermentation cost is saved;

本发明中,尾气数据与溶氧控制关联中,还包括以下内容:In the present invention, the correlation between the tail gas data and the dissolved oxygen control also includes the following content:

i)通过前期试验确定最低溶氧界限为25%,发酵系统中设置最低溶氧控制值为25%;i) The minimum dissolved oxygen limit is determined to be 25% through the preliminary test, and the minimum dissolved oxygen control value is set to 25% in the fermentation system;

ii)以尾气分析数据确定风量与搅拌的协调关系,通过分析尾气数据及发酵过程指标,确定先提风量还是先调转速,分析发酵成本,并通过实验数据反映调节方式的影响,以不影响发酵转化率为基础,确定最优的调整方案;ii) Determine the coordination relationship between the air volume and stirring based on the exhaust gas analysis data. By analyzing the exhaust gas data and fermentation process indicators, determine whether to increase the air volume first or adjust the rotation speed first, analyze the fermentation cost, and reflect the influence of the adjustment method through the experimental data, so as not to affect the fermentation Based on the conversion rate, determine the optimal adjustment plan;

iii)更进一步的通过分析尾气数据,控制合适的氧气浓度和二氧化碳浓度,将风量与消耗连锁,根据糖流加速度调整风量供应,避免风量浪费,减少其他物质的积累,提高转化率,进而节省发酵成本。iii) Further by analyzing the exhaust gas data, control the appropriate oxygen concentration and carbon dioxide concentration, link the air volume with the consumption, adjust the air volume supply according to the sugar flow acceleration, avoid the waste of air volume, reduce the accumulation of other substances, improve the conversion rate, and then save the fermentation cost.

本发明,将发酵过程中的各项参数进行整合关联,将菌体量与产酸速率、碳源、氮源消耗速率,尾气分析数据与溶氧控制进行关联,实现发酵过程的自动控制、自动流加,最大限度的减少人工操作,实现智能化发酵。The invention integrates and correlates various parameters in the fermentation process, correlates the amount of bacteria with the acid production rate, carbon source, nitrogen source consumption rate, and tail gas analysis data and dissolved oxygen control, so as to realize automatic control and automatic control of the fermentation process. Flow addition minimizes manual operations and realizes intelligent fermentation.

尽管已经示出和描述了本发明的实施例,对于本领域的普通技术人员而言,可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型,本发明的范围由所附权利要求及其等同物限定。Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, and substitutions can be made in these embodiments without departing from the principle and spirit of the invention and modifications, the scope of the present invention is defined by the appended claims and their equivalents.

Claims (3)

1. A novel lysine intelligent biological fermentation method is characterized in that: the process comprises the following steps:
1) the biomass of the thalli is related to the concentration of an acid-producing stream, the addition of a carbon source stream and the addition of a nitrogen source stream:
s1, detecting the thallus amount on line by using a microorganism concentration on-line analyzer, acquiring the concentration of the microorganisms in the fermentation tank in real time, and sequentially marking the acquired values as W1、W2、W3...Wn
S2, analyzing the biomass of the thalli, the concentration of an acid produced, the addition of a carbon source flow and the addition of a nitrogen source flow in different periods by theoretically analyzing the obtained large batch of test data, and sequentially obtaining the biomass of the thalli U, the concentration of the acid produced K, the addition of the carbon source flow C and the addition of the nitrogen source flow V;
s3, according to the analysis, the biomass of the thalli is related to the concentration of an acid-producing liquid, the adding amount of a carbon source liquid and the adding amount of a nitrogen source liquid, and different control standards are determined for different fermentation periods;
2) tail gas data is associated with dissolved oxygen control:
s1, analyzing the oxygen content and the carbon dioxide content in the fermentation tail gas by combining with an online tail gas analyzer to obtain an analysis result, wherein the content of the marked oxygen is L1Carbon dioxide content L2
S2, according to the analysis results of the oxygen content and the carbon dioxide content, obtaining the lysine fermentation oxygen consumption rate, the carbon dioxide production rate and the respiratory quotient, and directly reflecting the change condition of the lysine metabolic process through the content of oxygen and carbon dioxide in tail gas;
s3, sequentially changing different fermentation conditions, controlling one variable, analyzing the change condition of the tail gas, and obtaining the influence result of the fermentation conditions on the fermentation yield and the conversion rate of the lysine by combining the change of indexes of the fermentation process;
and S4, according to the result, associating the tail gas data with dissolved oxygen control, and correspondingly adjusting the fermentation control conditions.
2. The intelligent new lysine biofermentation method of claim 1, wherein: the correlation between the thallus biomass and the acid production concentration, the adding amount of the carbon source flow and the adding amount of the nitrogen source flow also comprises the following contents:
i) the method takes the rise of dissolved oxygen after the consumption of the bottom sugar as a control starting point, the thalli are in the logarithmic growth phase at the moment, the increase of the thalli amount is relatively quick, the sugar consumption is increased, the acid production rate is increased, after the thalli enter a stabilization period, the sugar consumption is stable, the acid production rate is stable, and then enter a fermentation later period, the carbon source consumption is reduced, and the acid production rate is reduced;
ii) establishing different stages of feeding formulas through experimental analysis, and obtaining feeding coefficients of different fermentation periods through calculation according to the control experience of early-stage artificial feeding to realize the automatic correlation of the biomass of the thalli and the feeding amount of the carbon source, wherein the calculation formula is as follows:
a=c*v+d+p;
wherein a is the sugar feeding rate (t/m)3·h);
c is a constant;
v is the increase of cell per unit (g/m)3·h);
d is the sugar consumption rate (t/m)3·h);
p is residual sugar control (5 g/L);
iii) correlating the nitrogen source flow rate with the carbon source flow rate according to the nitrogen source consumption level in different periods, and obtaining the carbon/nitrogen ratio in different periods according to the previous test to realize the automatic correlation of the nitrogen source flow rate and the carbon source flow rate;
iv) according to the calculated feeding coefficient, correlating all parameters in a control system to realize the correlation of the biomass of the thalli with the feeding amount of the carbon source and the feeding amount of the nitrogen source flow and realize automatic control.
3. The intelligent new lysine biofermentation method of claim 1, wherein: the tail gas data and dissolved oxygen control association also comprises the following contents:
i) the lowest dissolved oxygen limit is determined to be 25% through earlier stage tests, and the lowest dissolved oxygen control value is set to be 25% in a fermentation system;
ii) determining a coordination relation between air volume and stirring by using tail gas analysis data, determining whether air volume is increased or rotating speed is adjusted firstly by analyzing tail gas data and fermentation process indexes, analyzing fermentation cost, reflecting the influence of an adjusting mode by using experimental data, and determining an optimal adjusting scheme on the basis of not influencing fermentation conversion rate;
iii) further controlling proper oxygen concentration and carbon dioxide concentration by analyzing tail gas data, linking air quantity and consumption, and adjusting air quantity supply according to sugar stream acceleration.
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