生物基1， 3-丙二醇连续发酵过程的稳态分析与反馈控制

doi:10.11949/0438-1157.20211688

化工学报 ›› 2022, Vol. 73 ›› Issue (5): 2094-2100.DOI: 10.11949/0438-1157.20211688

生物基1， 3-丙二醇连续发酵过程的稳态分析与反馈控制

潘多涛¹(),王旭东³,史洪岩¹,修志龙²()

^1.沈阳化工大学信息工程学院，辽宁省化工过程控制技术重点实验室，辽宁沈阳 110142
^2.大连理工大学生物工程学院，辽宁大连 116024
^3.浙江工业大学药学院，浙江杭州 310014

收稿日期:2021-11-26 修回日期:2022-02-07 出版日期:2022-05-05 发布日期:2022-05-24
通讯作者: 修志龙
作者简介:潘多涛（1979—），男，博士，副教授，panduotao@syuct.edu.cn
基金资助:
辽宁省教育厅科研面上项目(LJKZ0433);国家自然科学基金项目(22078042);浙江省自然科学基金项目(LY21B060007)

Steady-state analysis and feedback control of continuous fermentation for bio-based 1, 3-propanediol

Duotao PAN¹(),Xudong WANG³,Hongyan SHI¹,Zhilong XIU²()

^1.Chemical Control Technology Key Laboratory of Liaoning Province, Institute of Information and Engineering, Shenyang University of Chemical and Technology, Shenyang 110142, Liaoning, China
^2.School of Bioengineering, Dalian University of Technology, Dalian 116024, Liaoning, China
^3.College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China

Received:2021-11-26 Revised:2022-02-07 Online:2022-05-05 Published:2022-05-24
Contact: Zhilong XIU

摘要/Abstract

摘要：

生物发酵甘油生产1,3-丙二醇的自动化控制是其工业化应用亟待解决的关键问题。首先，采用数学函数连续性分析深入研究了克雷伯氏杆菌连续发酵甘油生产1,3-丙二醇过程的多稳态特性。在不同的初始甘油浓度或稀释速率下，系统均会出现多稳态现象，通过双因素分析确定了多稳态出现的临界区域，该区域内部的稳态是不稳定的。之后，基于反馈控制理论和多稳态分析结果，设计优化了受残余甘油和产物浓度影响的稀释速率控制策略。在连续发酵过程中，调整时间从81.27 h缩短到34.11 h，显著提高了发酵初期阶段甘油的利用率；同时甘油转化率由0.478 mmol·mmol^-1提高至0.563 mmol·mmol^-1，生产强度由85.70 mmol·L^-1·h^-1提高到101.10 mmol·L^-1·h^-1，显著提高了生产性能。

关键词: 克雷伯氏杆菌, 甘油生物歧化, 1,3-丙二醇, 多稳态, 反馈控制

Abstract:

The automatic control of biologically fermented glycerol to produce 1,3-propanediol is the key problem to be solved in its industrial application. First, according to the mathematical model of the fermentation for Klebsiella pneumoniae to produce 1,3-propanediol, the multi-steady characteristics of continuous process were studied through the numerical continuation analysis for mathematical functions. Thereby, it was found that under different initial glycerol concentration or dilution rate, the system exhibited multi-steady state phenomenon. Through two-factor analysis, the critical region where multi-steady state occurs was determined, and the steady state in this region was unstable. After that, based on the feedback control theory and the results of multi-stability, the dilution rate control strategy affected by the concentration of residual glycerol and product 1,3-propanediol was designed. In the continuous fermentation, the settling time was shortened from 81.27 h to 34.11 h, which could significantly reduce the loss of glycerol in the early stage of fermentation. Meanwhile, the yield of 1,3-propanediol was increased from 0.478 mmol·mmol^-1 to 0.563 mmol·mmol^-1 and the production productivity was increased from 85.70 mmol·L^-1·h^-1 to 101.10 mmol·L^-1·h^-1. The results showed that the feedback control of the dilution rate significantly improved production performance, which can be adopted as a feeding guide for continuous culture in practice.

Key words: Klebsiella pneumoniae, glycerol dissimilation, 1,3-propanediol, multi-steady state, feedback control

中图分类号:

TQ 923

潘多涛, 王旭东, 史洪岩, 修志龙. 生物基1， 3-丙二醇连续发酵过程的稳态分析与反馈控制[J]. 化工学报, 2022, 73(5): 2094-2100.

Duotao PAN, Xudong WANG, Hongyan SHI, Zhilong XIU. Steady-state analysis and feedback control of continuous fermentation for bio-based 1, 3-propanediol[J]. CIESC Journal, 2022, 73(5): 2094-2100.

图/表 5

表1 克雷伯氏杆菌发酵模型的参数

Table 1 Parameter values in model for fermentation by K. pneumoniae

Parameter	Value	Unit	Parameter	Value	Unit
$μ m$	0.67	h^-1	$Y P D O m$	67.69	mmol·g^-1
$K S$	0.28	mmol·L^-1	$Δ q P D O m$	26.59	mmol·g^-1·h^-1
$C S *$	2039	mmol·L^-1	$K P D O *$	15.50	mmol·L^-1
$C P D O *$	939.5	mmol·L^-1	$m H A c$	-0.97	mmol·g^-1·h^-1
$C H A c *$	1026	mmol·L^-1	$Y H A c m$	33.07	mmol·g^-1
$C E t O H *$	360.9	mmol·L^-1	$Δ q H A c m$	5.74	mmol·g^-1·h^-1
$m S$	2.20	mmol·g^-1·h^-1	$K H A c *$	85.71	mmol·L^-1
$Y S m$	0.0082	g·mmol^-1	$b 1$	0.025	mmol·L^-1·h^-1
$Δ q S m$	28.58	mmol·g^-1·h^-1	$b 2$	5.18	mmol·L^-1·h^-1
$K S *$	11.43	mmol·L^-1	$c 1$	0.06	mmol·L^-1·h^-1
$m P D O$	-2.69	mmol·g^-1·h^-1	$c 2$	50.45	mmol·L^-1·h^-1

表1 克雷伯氏杆菌发酵模型的参数

Table 1 Parameter values in model for fermentation by K. pneumoniae

Parameter	Value	Unit	Parameter	Value	Unit
$μ m$	0.67	h^-1	$Y P D O m$	67.69	mmol·g^-1
$K S$	0.28	mmol·L^-1	$Δ q P D O m$	26.59	mmol·g^-1·h^-1
$C S *$	2039	mmol·L^-1	$K P D O *$	15.50	mmol·L^-1
$C P D O *$	939.5	mmol·L^-1	$m H A c$	-0.97	mmol·g^-1·h^-1
$C H A c *$	1026	mmol·L^-1	$Y H A c m$	33.07	mmol·g^-1
$C E t O H *$	360.9	mmol·L^-1	$Δ q H A c m$	5.74	mmol·g^-1·h^-1
$m S$	2.20	mmol·g^-1·h^-1	$K H A c *$	85.71	mmol·L^-1
$Y S m$	0.0082	g·mmol^-1	$b 1$	0.025	mmol·L^-1·h^-1
$Δ q S m$	28.58	mmol·g^-1·h^-1	$b 2$	5.18	mmol·L^-1·h^-1
$K S *$	11.43	mmol·L^-1	$c 1$	0.06	mmol·L^-1·h^-1
$m P D O$	-2.69	mmol·g^-1·h^-1	$c 2$	50.45	mmol·L^-1·h^-1

图1 发酵过程中不同稀释速率下的多稳态现象及其临界区域

Fig.1 Multistability phenomenon and its critical region at different dilution rates during fermentation

图2 不同稀释速率策略下的模拟结果对比

Fig.2 Comparison of simulation results under different strategies for dilution rate

表2 不同稀释速率策略下的稳态值对比

Table 2 Comparison of steady values of metabolites under different strategies for dilution rate

Strategy for dilution rate

Biomass/

(g·L^-1)

Glycerol/

(mmol·L^-1)

PDO/

(mmol·L^-1)

EtOH/

(mmol·L^-1)

HAc/

(mmol·L^-1)

图3 受控稀释速率的变化过程

Fig.3 Variation of the controlled dilution rate during the fermentation

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生物基1， 3-丙二醇连续发酵过程的稳态分析与反馈控制

Steady-state analysis and feedback control of continuous fermentation for bio-based 1, 3-propanediol

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