Large-scale kinetic metabolic models of Pseudomonas putida KT2440 for consistent design of metabolic engineering strategies

恶臭假单胞菌 代谢工程 通量平衡分析 稳健性(进化) 有机体 代谢通量分析 生物系统 计算生物学 焊剂(冶金) 代谢途径 代谢网络 化学 合成生物学 生物过程 新陈代谢 生物 系统生物学 生物化学 生化工程 遗传学 基因 有机化学 工程类
作者
Milenko Tokic,Vassily Hatzimanikatis,Ljubiša Mišković
出处
期刊:Biotechnology for Biofuels [Springer Nature]
卷期号:13 (1) 被引量:34
标识
DOI:10.1186/s13068-020-1665-7
摘要

Abstract Background Pseudomonas putida is a promising candidate for the industrial production of biofuels and biochemicals because of its high tolerance to toxic compounds and its ability to grow on a wide variety of substrates. Engineering this organism for improved performances and predicting metabolic responses upon genetic perturbations requires reliable descriptions of its metabolism in the form of stoichiometric and kinetic models. Results In this work, we developed kinetic models of P. putida to predict the metabolic phenotypes and design metabolic engineering interventions for the production of biochemicals. The developed kinetic models contain 775 reactions and 245 metabolites. Furthermore, we introduce here a novel set of constraints within thermodynamics-based flux analysis that allow for considering concentrations of metabolites that exist in several compartments as separate entities. We started by a gap-filling and thermodynamic curation of iJN1411, the genome-scale model of P. putida KT2440. We then systematically reduced the curated iJN1411 model, and we created three core stoichiometric models of different complexity that describe the central carbon metabolism of P. putida . Using the medium complexity core model as a scaffold, we generated populations of large-scale kinetic models for two studies. In the first study, the developed kinetic models successfully captured the experimentally observed metabolic responses to several single-gene knockouts of a wild-type strain of P. putida KT2440 growing on glucose. In the second study, we used the developed models to propose metabolic engineering interventions for improved robustness of this organism to the stress condition of increased ATP demand. Conclusions The study demonstrates the potential and predictive capabilities of the kinetic models that allow for rational design and optimization of recombinant P. putida strains for improved production of biofuels and biochemicals. The curated genome-scale model of P. putida together with the developed large-scale stoichiometric and kinetic models represents a significant resource for researchers in industry and academia.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
dww发布了新的文献求助10
1秒前
1秒前
忙碌的数学人完成签到,获得积分10
2秒前
Ade阿德完成签到,获得积分10
2秒前
caicai完成签到,获得积分10
2秒前
3秒前
4秒前
4秒前
4秒前
kevin1018完成签到,获得积分10
4秒前
叮当应助小鸡炖蘑菇采纳,获得10
5秒前
5秒前
5秒前
等等发布了新的文献求助10
6秒前
7秒前
胡胡胡upupup完成签到,获得积分10
7秒前
霸气土豆完成签到 ,获得积分10
8秒前
8秒前
舒适静丹完成签到,获得积分20
8秒前
明亮靖柔完成签到,获得积分10
9秒前
哦啦啦发布了新的文献求助10
9秒前
科研通AI2S应助ikun0000采纳,获得10
10秒前
tachang完成签到,获得积分10
10秒前
糖果发布了新的文献求助10
10秒前
Yukiiiii发布了新的文献求助10
11秒前
舒适静丹发布了新的文献求助10
11秒前
一起来读paper啊完成签到,获得积分10
13秒前
Benjamin完成签到 ,获得积分10
14秒前
yuan发布了新的文献求助10
15秒前
15秒前
Niuma完成签到,获得积分10
16秒前
17秒前
17秒前
盈月发布了新的文献求助10
17秒前
我是老大应助舒适静丹采纳,获得10
18秒前
香蕉觅云应助panpan2采纳,获得10
20秒前
李李发布了新的文献求助10
21秒前
Orange应助nn采纳,获得10
21秒前
天天快乐应助JKIKU采纳,获得10
21秒前
神勇芷蝶Jelly完成签到,获得积分10
22秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
China's Relations With Japan 1945-83: The Role of Liao Chengzhi 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3149266
求助须知:如何正确求助?哪些是违规求助? 2800354
关于积分的说明 7839707
捐赠科研通 2457979
什么是DOI,文献DOI怎么找? 1308158
科研通“疑难数据库(出版商)”最低求助积分说明 628456
版权声明 601706