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 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.

Metabolic engineering of glycosylated polyketide biosynthesis

2018 ◽  
Vol 2 (3) ◽  
pp. 389-403 ◽  
Author(s):  
Ramesh Prasad Pandey ◽  
Prakash Parajuli ◽  
Jae Kyung Sohng
Keyword(s):  
Natural Products ◽  
Metabolic Engineering ◽  
Value Added ◽  
Chemical Diversity ◽  
Yeast Cells ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Modification Method ◽  
Post Modification ◽  
Microbial Biosynthesis

Microbial cell factories are extensively used for the biosynthesis of value-added chemicals, biopharmaceuticals, and biofuels. Microbial biosynthesis is also realistic for the production of heterologous molecules including complex natural products of plant and microbial origin. Glycosylation is a well-known post-modification method to engineer sugar-functionalized natural products. It is of particular interest to chemical biologists to increase chemical diversity of molecules. Employing the state-of-the-art systems and synthetic biology tools, a range of small to complex glycosylated natural products have been produced from microbes using a simple and sustainable fermentation approach. In this context, this review covers recent notable metabolic engineering approaches used for the biosynthesis of glycosylated plant and microbial polyketides in different microorganisms. This review article is broadly divided into two major parts. The first part is focused on the biosynthesis of glycosylated plant polyketides in prokaryotes and yeast cells, while the second part is focused on the generation of glycosylated microbial polyketides in actinomycetes.

scholarly journals In Silico Design for Systems-Based Metabolic Engineering In Escherichia Coli for The Bioconversion of Aerobic Glycerol to Succinic Acid

2020 ◽  
Author(s):  
Albert Enrique Tafur Rangel ◽  
Wendy Lorena Rios Guzman ◽  
Carmen Elvira Ojeda Cuella ◽  
Daissy Esther Mejia Perez ◽  
Ross Carlson ◽  
...  
Keyword(s):  
Machine Learning ◽  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Succinic Acid ◽  
In Silico ◽  
Rational Design ◽  
Industrial Biotechnology ◽  
E Coli ◽  
Cell Factories ◽  
Transcriptomics Data

Abstract BackgroundGlycerol has become an interesting carbon source for industrial processes as consequence of the biodiesel business growth since it has shown promising results in terms of biomass/substrate yields. Selecting the appropriate metabolic targets to build efficient cell factories and maximize the desired chemical production in as little time as possible is a major challenge in industrial biotechnology. The engineering of microbial metabolism following rational design has been widely studied. However, it is a cost-, time-, and laborious-intensive process because of the cell network complexity; thus, to be proficient is needed known in advance the effects of gene deletions.ResultsAn in silico experiment was performed to model and understand the effects of metabolic engineering over the metabolism by transcriptomics data integration. In this study, systems-based metabolic engineering to predict the metabolic engineering targets was used in order to increase the bioconversion of glycerol to succinic acid by Escherichia coli. Transcriptomics analysis suggest insights of how increase the glycerol utilization of the cell for further design efficient cell factories. Three models were used; an E. coli core model, a model obtained after the integration of transcriptomics data obtained from E. coli growing in an optimized culture media, and a third one obtained after integration of transcriptomics data obtained from E. coli after adaptive laboratory evolution experiments. A total of 2402 strains were obtained from these three models. Fumarase and pyruvate dehydrogenase were frequently predicted in all the models, suggesting that these reactions are essential to increasing succinic acid production from glycerol. Finally, using flux balance analysis results for all the mutants predicted, a machine learning method was developed to predict new mutants as well as to propose optimal metabolic engineering targets and mutants based on the measurement of importance of each knockout’s (feature’s) contribution.ConclusionsThe combination of transcriptome, systems metabolic modeling, and machine learning analyses revealed versatile molecular mechanisms involved in the utilization of glycerol. These data provide a platform to improve the prediction of metabolic engineering targets to design efficient cell factories. Our results may also work a guide platform for the selection/engineering of microorganisms for production of interesting chemical compounds.

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 Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli

2016 ◽  
Vol 113 (12) ◽  
pp. 3209-3214 ◽  
Author(s):  
Bradley Walters Biggs ◽  
Chin Giaw Lim ◽  
Kristen Sagliani ◽  
Smriti Shankar ◽  
Gregory Stephanopoulos ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Natural Products ◽  
Metabolic Engineering ◽  
Biosynthetic Pathway ◽  
Complex Molecules ◽  
E Coli ◽  
Precursor Synthesis ◽  
P450 Expression ◽  
High Level

Recent advances in metabolic engineering have demonstrated the potential to exploit biological chemistry for the synthesis of complex molecules. Much of the progress to date has leveraged increasingly precise genetic tools to control the transcription and translation of enzymes for superior biosynthetic pathway performance. However, applying these approaches and principles to the synthesis of more complex natural products will require a new set of tools for enabling various classes of metabolic chemistries (i.e., cyclization, oxygenation, glycosylation, and halogenation) in vivo. Of these diverse chemistries, oxygenation is one of the most challenging and pivotal for the synthesis of complex natural products. Here, using Taxol as a model system, we use nature’s favored oxygenase, the cytochrome P450, to perform high-level oxygenation chemistry in Escherichia coli. An unexpected coupling of P450 expression and the expression of upstream pathway enzymes was discovered and identified as a key obstacle for functional oxidative chemistry. By optimizing P450 expression, reductase partner interactions, and N-terminal modifications, we achieved the highest reported titer of oxygenated taxanes (∼570 ± 45 mg/L) in E. coli. Altogether, this study establishes E. coli as a tractable host for P450 chemistry, highlights the potential magnitude of protein interdependency in the context of synthetic biology and metabolic engineering, and points to a promising future for the microbial synthesis of complex chemical entities.

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