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 Construction and optimization of microbial cell factories for sustainable production of bioactive dammarenediol-II glucosides

2019 ◽  
Vol 21 (12) ◽  
pp. 3286-3299 ◽  
Author(s):  
Zong-Feng Hu ◽  
An-Di Gu ◽  
Lan Liang ◽  
Yan Li ◽  
Ting Gong ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Industrial Production ◽  
Sustainable Production ◽  
Microbial Cell ◽  
Microbial Cell Factories ◽  
Cell Factories

A green and sustainable approach is established by metabolic engineering for industrial production of bioactive dammarenediol-II glucosides.

scholarly journals Synthesizing ginsenoside Rh2 in Saccharomyces cerevisiae cell factory at high-efficiency

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Pingping Wang ◽  
Wei Wei ◽  
Wei Ye ◽  
Xiaodong Li ◽  
Wenfang Zhao ◽  
...  
Keyword(s):  
Yeast Cell ◽  
Batch Fermentation ◽  
Cell Factory ◽  
Ginsenoside Rh2 ◽  
Fed Batch ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Fed Batch Fermentation ◽  
Shake Flasks ◽  
Produce Plant

AbstractSynthetic biology approach has been frequently applied to produce plant rare bioactive compounds in microbial cell factories by fermentation. However, to reach an ideal manufactural efficiency, it is necessary to optimize the microbial cell factories systemically by boosting sufficient carbon flux to the precursor synthesis and tuning the expression level and efficiency of key bioparts related to the synthetic pathway. We previously developed a yeast cell factory to produce ginsenoside Rh2 from glucose. However, the ginsenoside Rh2 yield was too low for commercialization due to the low supply of the ginsenoside aglycone protopanaxadiol (PPD) and poor performance of the key UDP-glycosyltransferase (UGT) (biopart UGTPg45) in the final step of the biosynthetic pathway. In the present study, we constructed a PPD-producing chassis via modular engineering of the mevalonic acid pathway and optimization of P450 expression levels. The new yeast chassis could produce 529.0 mg/L of PPD in shake flasks and 11.02 g/L in 10 L fed-batch fermentation. Based on this high PPD-producing chassis, we established a series of cell factories to produce ginsenoside Rh2, which we optimized by improving the C3–OH glycosylation efficiency. We increased the copy number of UGTPg45, and engineered its promoter to increase expression levels. In addition, we screened for more efficient and compatible UGT bioparts from other plant species and mutants originating from the direct evolution of UGTPg45. Combining all engineered strategies, we built a yeast cell factory with the greatest ginsenoside Rh2 production reported to date, 179.3 mg/L in shake flasks and 2.25 g/L in 10 L fed-batch fermentation. The results set up a successful example for improving yeast cell factories to produce plant rare natural products, especially the glycosylated ones.

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 De Novo Biosynthesis of C-Arabinosylated Flavones by Utilization of Indica Rice C-Glycosyltransferases

2021 ◽  
Author(s):  
Zhuo Chen ◽  
Yuwei Sun ◽  
Guangyi Wang ◽  
Ying Zhang ◽  
Qian Zhang ◽  
...  
Keyword(s):  
De Novo ◽  
Indica Rice ◽  
Fed Batch ◽  
Rice Varieties ◽  
E Coli ◽  
De Novo Biosynthesis ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Fed Batch Fermentation ◽  
Heterologous Pathway

Abstract Flavone C-arabinosides/xylosides are plant-originated glycoconjugates with various bioactivities. However, the potential utility of these molecules is hindered by their low abundance in nature. Engineering biosynthesis pathway in heterologous bacterial chassis provides a sustainable source of these C-glycosides. We previously reported bifunctional C-glucosyl/C-arabinosyltransferases in Oryza sativa japonica and O. sativa indica, which influence the C-glycoside spectrum in different rice varieties. In this study, we proved the C-arabinosyltransferring activity of rice C-glycosyltransferases (CGTs) on the mono-C-glucoside substrate nothofagin, followed by taking advantage of specific CGTs and introducing heterologous UDP-pentose supply, to realize the production of eight different C-arabinosides/xylosides in recombinant E. coli. Fed-batch fermentation and precursor supplement maximized the titer of rice-originated C-arabinosides to 20~110 mg/L in an E. coli chassis. The optimized final titer of schaftoside and apigenin di-C-arabinoside reached 19.87 and 113.16 mg/L respectively. We demonstrate here the success of de novo bio-production of C-arabinosylated and C-xylosylated flavones by heterologous pathway reconstitution. These results lay a foundation for further optimal manufacture of complex flavonoid compounds in microbial cell factories.

Semi-industrial scale (30 m3) fed-batch fermentation for the production of d-lactate by Escherichia coli strain HBUT-D15

2016 ◽  
Vol 44 (2) ◽  
pp. 221-228 ◽  
Author(s):  
Xiangmin Fu ◽  
Yongze Wang ◽  
Jinhua Wang ◽  
Erin Garza ◽  
Ryan Manow ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Batch Fermentation ◽  
Coli Strain ◽  
Industrial Scale ◽  
Fed Batch ◽  
Fed Batch Fermentation

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 De novo biosynthesis of C-arabinosylated flavones by utilization of indica rice C-glycosyltransferases

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Zhuo Chen ◽  
Yuwei Sun ◽  
Guangyi Wang ◽  
Ying Zhang ◽  
Qian Zhang ◽  
...  
Keyword(s):  
De Novo ◽  
Indica Rice ◽  
Fed Batch ◽  
Rice Varieties ◽  
E Coli ◽  
De Novo Biosynthesis ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Fed Batch Fermentation ◽  
Heterologous Pathway

AbstractFlavone C-arabinosides/xylosides are plant-originated glycoconjugates with various bioactivities. However, the potential utility of these molecules is hindered by their low abundance in nature. Engineering biosynthesis pathway in heterologous bacterial chassis provides a sustainable source of these C-glycosides. We previously reported bifunctional C-glucosyl/C-arabinosyltransferases in Oryza sativa japonica and O. sativa indica, which influence the C-glycoside spectrum in different rice varieties. In this study, we proved the C-arabinosyl-transferring activity of rice C-glycosyltransferases (CGTs) on the mono-C-glucoside substrate nothofagin, followed by taking advantage of specific CGTs and introducing heterologous UDP-pentose supply, to realize the production of eight different C-arabinosides/xylosides in recombinant E. coli. Fed-batch fermentation and precursor supplement maximized the titer of rice-originated C-arabinosides to 20–110 mg/L in an E. coli chassis. The optimized final titer of schaftoside and apigenin di-C-arabinoside reached 19.87 and 113.16 mg/L, respectively. We demonstrate here the success of de novo bio-production of C-arabinosylated and C-xylosylated flavones by heterologous pathway reconstitution. These results lay a foundation for further optimal manufacture of complex flavonoid compounds in microbial cell factories.

scholarly journals Metabolic engineering strategy for synthetizing trans-4-hydroxy-l-proline in microorganisms

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenyu Zhang ◽  
Pengfu Liu ◽  
Weike Su ◽  
Huawei Zhang ◽  
Wenqian Xu ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Biosynthetic Pathway ◽  
Industrial Applications ◽  
Microbial Cell Factories ◽  
Important Amino Acid ◽  
Cell Factories ◽  
Complex Process ◽  
Engineering Strategy ◽  
Hydrolysis Of ◽  
New Strategies

AbstractTrans-4-hydroxy-l-proline is an important amino acid that is widely used in medicinal and industrial applications, particularly as a valuable chiral building block for the organic synthesis of pharmaceuticals. Traditionally, trans-4-hydroxy-l-proline is produced by the acidic hydrolysis of collagen, but this process has serious drawbacks, such as low productivity, a complex process and heavy environmental pollution. Presently, trans-4-hydroxy-l-proline is mainly produced via fermentative production by microorganisms. Some recently published advances in metabolic engineering have been used to effectively construct microbial cell factories that have improved the trans-4-hydroxy-l-proline biosynthetic pathway. To probe the potential of microorganisms for trans-4-hydroxy-l-proline production, new strategies and tools must be proposed. In this review, we provide a comprehensive understanding of trans-4-hydroxy-l-proline, including its biosynthetic pathway, proline hydroxylases and production by metabolic engineering, with a focus on improving its production.

A dynamic metabolic flux balance based model of fed-batch fermentation ofbordetella pertussis

2013 ◽  
Vol 29 (2) ◽  
pp. 520-531 ◽  
Author(s):  
Hector Budman ◽  
Nilesh Patel ◽  
Melih Tamer ◽  
Walid Al-Gherwi
Keyword(s):  
Batch Fermentation ◽  
Metabolic Flux ◽  
Fed Batch ◽  
Flux Balance ◽  
Fed Batch Fermentation ◽  
Ofbordetella Pertussis
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