scholarly journals Computational Modelling of Metabolic Burden and Substrate Toxicity in Escherichia coli Carrying a Synthetic Metabolic Pathway

2019 ◽  
Vol 7 (11) ◽  
pp. 553 ◽  
Author(s):  
Martin Demko ◽  
Lukáš Chrást ◽  
Pavel Dvořák ◽  
Jiří Damborský ◽  
David Šafránek
Keyword(s):  
Escherichia Coli ◽  
Population Growth ◽  
Metabolic Pathway ◽  
Computational Modelling ◽  
Real Data ◽  
Coli Strain ◽  
Metabolic Burden ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Synthetic Metabolic Pathway

In our previous work, we designed and implemented a synthetic metabolic pathway for 1,2,3-trichloropropane (TCP) biodegradation in Escherichia coli. Significant effects of metabolic burden and toxicity exacerbation were observed on single cell and population levels. Deeper understanding of mechanisms underlying these effects is extremely important for metabolic engineering of efficient microbial cell factories for biotechnological processes. In this paper, we present a novel mathematical model of the pathway. The model addresses for the first time the combined effects of toxicity exacerbation and metabolic burden in the context of bacterial population growth. The model is calibrated with respect to the real data obtained with our original synthetically modified E. coli strain. Using the model, we explore the dynamics of the population growth along with the outcome of the TCP biodegradation pathway considering the toxicity exacerbation and metabolic burden. On the methodological side, we introduce a unique computational workflow utilising algorithmic methods of computer science for the particular modelling problem.

scholarly journals Enhancement of β-Alanine Biosynthesis in Escherichia coli Based on Multivariate Modular Metabolic Engineering

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1017
Author(s):  
Jian Xu ◽  
Li Zhou ◽  
Zhemin Zhou
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Industrial Production ◽  
Metabolic Flux ◽  
Coli Strain ◽  
Biosynthesis Pathway ◽  
Fed Batch ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Fed Batch Fermentation

β-alanine is widely used as an intermediate in industrial production. However, the low production of microbial cell factories limits its further application. Here, to improve the biosynthesis production of β-alanine in Escherichia coli, multivariate modular metabolic engineering was recruited to manipulate the β-alanine biosynthesis pathway through keeping the balance of metabolic flux among the whole metabolic network. The β-alanine biosynthesis pathway was separated into three modules: the β-alanine biosynthesis module, TCA module, and glycolysis module. Global regulation was performed throughout the entire β-alanine biosynthesis pathway rationally and systematically by optimizing metabolic flux, overcoming metabolic bottlenecks and weakening branch pathways. As a result, metabolic flux was channeled in the direction of β-alanine biosynthesis without huge metabolic burden, and 37.9 g/L β-alanine was generated by engineered Escherichia coli strain B0016-07 in fed-batch fermentation. This study was meaningful to the synthetic biology of β-alanine industrial production.

Escherichia coli as a platform microbial host for systems metabolic engineering

2021 ◽  
Author(s):  
Dongsoo Yang ◽  
Cindy Pricilia Surya Prabowo ◽  
Hyunmin Eun ◽  
Seon Young Park ◽  
In Jin Cho ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Metabolic Engineering ◽  
Food Ingredients ◽  
E Coli ◽  
Renewable Biomass ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Systems Metabolic Engineering ◽  
Microbial Host

Abstract Bio-based production of industrially important chemicals and materials from non-edible and renewable biomass has become increasingly important to resolve the urgent worldwide issues including climate change. Also, bio-based production, instead of chemical synthesis, of food ingredients and natural products has gained ever increasing interest for health benefits. Systems metabolic engineering allows more efficient development of microbial cell factories capable of sustainable, green, and human-friendly production of diverse chemicals and materials. Escherichia coli is unarguably the most widely employed host strain for the bio-based production of chemicals and materials. In the present paper, we review the tools and strategies employed for systems metabolic engineering of E. coli. Next, representative examples and strategies for the production of chemicals including biofuels, bulk and specialty chemicals, and natural products are discussed, followed by discussion on materials including polyhydroxyalkanoates (PHAs), proteins, and nanomaterials. Lastly, future perspectives and challenges remaining for systems metabolic engineering of E. coli are discussed.

scholarly journals Reverse engineering of fatty acid-tolerant Escherichia coli identifies design strategies for robust microbial cell factories

2020 ◽  
Vol 61 ◽  
pp. 120-130 ◽  
Author(s):  
Yingxi Chen ◽  
Erin E. Boggess ◽  
Efrain Rodriguez Ocasio ◽  
Aric Warner ◽  
Lucas Kerns ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Fatty Acid ◽  
Reverse Engineering ◽  
Microbial Cell ◽  
Design Strategies ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Acid Tolerant

scholarly journals ESCHERICHIA COLI REDOX MUTANTS AS MICROBIAL CELL FACTORIES FOR THE SYNTHESIS OF REDUCED BIOCHEMICALS

2012 ◽  
Vol 3 (4) ◽  
pp. e201210019 ◽  
Author(s):  
Jimena A. Ruiz ◽  
Alejandra de Almeida ◽  
Manuel S. Godoy ◽  
Mariela P. Mezzina ◽  
Gonzalo N. Bidart ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Microbial Cell ◽  
Microbial Cell Factories ◽  
Cell Factories

scholarly journals Engineering Escherichia coli biofilm to increase contact surface for shikimate and L-malate production

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Qiang Ding ◽  
Yadi Liu ◽  
Guipeng Hu ◽  
Liang Guo ◽  
Cong Gao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Contact Surface ◽  
Self Assembly ◽  
Cds Nanoparticles ◽  
Cellular Functions ◽  
E Coli ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Nanoparticles Concentration ◽  
Definition Of

AbstractMicrobial organelles are a promising model to promote cellular functions for the production of high-value chemicals. However, the concentrations of enzymes and nanoparticles are limited by the contact surface in single Escherichia coli cells. Herein, the definition of contact surface is to improve the amylase and CdS nanoparticles concentration for enhancing the substrate starch and cofactor NADH utilization. In this study, two biofilm-based strategies were developed to improve the contact surface for the production of shikimate and L-malate. First, the contact surface of E. coli was improved by amylase self-assembly with a blue light-inducible biofilm-based SpyTag/SpyCatcher system. This system increased the glucose concentration by 20.7% and the starch-based shikimate titer to 50.96 g L−1, which showed the highest titer with starch as substrate. Then, the contact surface of E. coli was improved using a biofilm-based CdS-biohybrid system by light-driven system, which improved the NADH concentration by 83.3% and increased the NADH-dependent L-malate titer to 45.93 g L−1. Thus, the biofilm-based strategies can regulate cellular functions to increase the efficiency of microbial cell factories based on the optogenetics, light-driven, and metabolic engineering. Graphical Abstract

scholarly journals De novo Biosynthesis of Tyrosol Acetate and Hydroxytyrosol Acetate from Glucose in Engineered Escherichia Coli

2021 ◽  
Author(s):  
Daoyi Guo ◽  
Xiao Fu ◽  
Yue Sun ◽  
Xun Li ◽  
Hong Pan
Keyword(s):  
Escherichia Coli ◽  
De Novo ◽  
Virgin Olive Oil ◽  
Carbon Sources ◽  
Acetate Production ◽  
E Coli ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Alcohol Acetyltransferase ◽  
First Time

Abstract Background: Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine. Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great significance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis.Results: In this study, two de novo biosynthetic pathways for the production of tyrosol acetate and hydroxytyrosol acetate were constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3-hydroxylase HpaBC.Conclusion: We have successfully established the artificial biosynthetic pathway of tyrosol acetate and hydroxytyrosol acetate from fermentable sugars and demonstrated for the first time the direct fermentative production of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered E. coli

scholarly journals Reprogramming microbial populations using a programmed lysis system to improve chemical production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenwen Diao ◽  
Liang Guo ◽  
Qiang Ding ◽  
Cong Gao ◽  
Guipeng Hu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Division Of Labor ◽  
Microbial Populations ◽  
Chemical Production ◽  
E Coli ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Phenotypic Structure ◽  
Colicin M ◽  
Butyrate Production

AbstractMicrobial populations are a promising model for achieving microbial cooperation to produce valuable chemicals. However, regulating the phenotypic structure of microbial populations remains challenging. In this study, a programmed lysis system (PLS) is developed to reprogram microbial cooperation to enhance chemical production. First, a colicin M -based lysis unit is constructed to lyse Escherichia coli. Then, a programmed switch, based on proteases, is designed to regulate the effective lysis unit time. Next, a PLS is constructed for chemical production by combining the lysis unit with a programmed switch. As a result, poly (lactate-co-3-hydroxybutyrate) production is switched from PLH synthesis to PLH release, and the content of free PLH is increased by 283%. Furthermore, butyrate production with E. coli consortia is switched from E. coli BUT003 to E. coli BUT004, thereby increasing butyrate production to 41.61 g/L. These results indicate the applicability of engineered microbial populations for improving the metabolic division of labor to increase the efficiency of microbial cell factories.

scholarly journals Metabolic Engineering Escherichia coli for the Production of Lycopene

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3136 ◽  
Author(s):  
Zhaobao Wang ◽  
JingXin Sun ◽  
Qun Yang ◽  
Jianming Yang
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Regulatory Networks ◽  
Carbon Sources ◽  
Operation Technique ◽  
Mva Pathway ◽  
E Coli ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Lycopene Production

Lycopene, a potent antioxidant, has been widely used in the fields of pharmaceuticals, nutraceuticals, and cosmetics. However, the production of lycopene extracted from natural sources is far from meeting the demand. Consequently, synthetic biology and metabolic engineering have been employed to develop microbial cell factories for lycopene production. Due to the advantages of rapid growth, complete genetic background, and a reliable genetic operation technique, Escherichia coli has become the preferred host cell for microbial biochemicals production. In this review, the recent advances in biological lycopene production using engineered E. coli strains are summarized: First, modification of the endogenous MEP pathway and introduction of the heterogeneous MVA pathway for lycopene production are outlined. Second, the common challenges and strategies for lycopene biosynthesis are also presented, such as the optimization of other metabolic pathways, modulation of regulatory networks, and optimization of auxiliary carbon sources and the fermentation process. Finally, the future prospects for the improvement of lycopene biosynthesis are also discussed.

scholarly journals Exacerbation of substrate toxicity by IPTG in Escherichia coli BL21(DE3) carrying a synthetic metabolic pathway

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Pavel Dvorak ◽  
Lukas Chrast ◽  
Pablo I. Nikel ◽  
Radek Fedr ◽  
Karel Soucek ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Pathway ◽  
Escherichia Coli Bl21 ◽  
Synthetic Metabolic Pathway

Contrasting effects of isocitrate dehydrogenase deletion on fluxes through enzymes of central metabolism in Escherichia coli

2019 ◽  
Vol 366 (15) ◽  
Author(s):  
Mansi El-Mansi
Keyword(s):  
Escherichia Coli ◽  
Pyruvate Kinase ◽  
High Throughput ◽  
Isocitrate Dehydrogenase ◽  
Krebs Cycle ◽  
Flux Analysis ◽  
Metabolic Fluxes ◽  
Acetate Excretion ◽  
Microbial Cell Factories ◽  
Cell Factories

ABSTRACT Flux analysis is central to understanding cellular metabolism and successful manipulation of metabolic fluxes in microbial cell-factories. Isocitrate dehydrogenase (ICDH) deletion conferred contrasting effects on fluxes through substrate-level phosphorylation (SLP) reactions. While significantly increasing flux through pyruvate kinase, it diminishes flux through succinyl CoA synthetase and upregulates phosphotransacetylase (PTA) and acetate kinase (AK). In addition to acetate, the ICDH-less strain excretes pyruvate, citrate and isocitrate. While efflux to acetate excretion by the Escherichia coli parental strain and its ICDH-less derivative is a reflection of high throughput of glycolytic intermediates, excretion of pyruvate is a reflection of high throughput via pyruvate kinase. On the other hand, citrate and isocitrate excretion is a reflection of truncating the Krebs cycle at the level of ICDH. Furthermore, another striking finding is the inability of the ICDH-less cultures to utilize acetate as a source of carbon despite the availability of an adequate supply of extracellular glutamate (for biosynthesis) and elevated levels of AK and PTA (for acetate uptake). This striking observation is now explicable in the light of the newly proposed hypothesis that the expression of the ace operon enzymes is controlled in response to a minimum threshold signal (ATP), which could not be achieved in the ICDH-less strain.

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