Systems metabolic engineering of Escherichia coli to enhance the production of flavonoid glucuronides

RSC Advances ◽  
2016 ◽  
Vol 6 (40) ◽  
pp. 33622-33630 ◽  
Author(s):  
Yan Yang ◽  
Hui-Min Wang ◽  
Yuan-Feng Tong ◽  
Min-Zhi Liu ◽  
Ke-Di Cheng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Biosynthetic Pathway ◽  
Systems Metabolic Engineering ◽  
Engineered Strain

Through modulating UDPGA biosynthetic pathway and introducting SbUGT, an engineered strain was constructed to enhance the production of flavonoid glucuronides.

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.

Systems metabolic engineering of Escherichia coli for production of the antitumor drugs violacein and deoxyviolacein

2013 ◽  
Vol 20 ◽  
pp. 29-41 ◽  
Author(s):  
André L. Rodrigues ◽  
Nathalie Trachtmann ◽  
Judith Becker ◽  
Ananta F. Lohanatha ◽  
Jana Blotenberg ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Antitumor Drugs ◽  
Systems Metabolic Engineering

scholarly journals Transport engineering for improving production and secretion of valuable alkaloids in Escherichia coli

2021 ◽  
Author(s):  
Yasuyuki Yamada ◽  
Miya Urui ◽  
Hidehiro Oki ◽  
Kai Inoue ◽  
Haruyuki Matsui ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Biosynthetic Pathway ◽  
Plasmid Stability ◽  
Plant Metabolites ◽  
E Coli ◽  
Specialized Metabolites ◽  
Important Intermediate ◽  
High Production ◽  
Suitable Expression

AbstractMetabolic engineering of microorganisms to produce specialized plant metabolites has been established. However, these methods are limited by low productivity and the intracellular accumulation of metabolites. Here, we aimed to use transport engineering for producing reticuline, an important intermediate in the alkaloid biosynthetic pathway. We established a reticuline-producing Escherichia coli strain and introduced a multidrug and toxic compound extrusion transporter, Arabidopsis AtDTX1, into it. AtDTX1 was selected due to its suitable expression in E. coli and its reticuline-transport activity. Expression of AtDTX1 significantly enhanced reticuline production by 11-fold; produced reticuline was secreted into the medium. AtDTX1 expression conferred high plasmid stability, and up- or downregulated genes associated with biological processes including metabolic pathways for reticuline biosynthesis, leading to a high production and secretion of reticuline. The successful application of a transporter for alkaloid production suggests that the transport engineering approach may improve the biosynthesis of specialized metabolites via metabolic engineering.

scholarly journals Metabolic engineering of Escherichia coli for de novo biosynthesis of vitamin B12

2018 ◽  
Author(s):  
Huan Fang ◽  
Dong Li ◽  
Jie Kang ◽  
Pingtao Jiang ◽  
Jibin Sun ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Biosynthetic Pathway ◽  
Rhodobacter Capsulatus ◽  
De Novo ◽  
Vitamin B ◽  
E Coli ◽  
De Novo Biosynthesis ◽  
Optimization Of Fermentation ◽  
Aerobic And Anaerobic

ABSTRACTThe only known source of vitamin B12 (adenosylcobalamin) is from bacteria and archaea, and the only unknown step in its biosynthesis is the production of the intermediate adenosylcobinamide phosphate. Here, using genetic and metabolic engineering, we generated an Escherichia coli strain that produces vitamin B12 via an engineered de novo aerobic biosynthetic pathway. Excitingly, the BluE and CobC enzymes from Rhodobacter capsulatus transform L-threonine into (R)-1-Amino-2-propanol O-2-Phosphate, which is then condensed with adenosylcobyric acid to yield adenosylcobinamide phosphate by either CobD from the aeroic R. capsulatus or CbiB from the anerobic Salmonella typhimurium. These findings suggest that the biosynthetic steps from co(II)byrinic acid a,c-diamide to adocobalamin are the same in both the aerobic and anaerobic pathways. Finally, we increased the vitamin B12 yield of a recombinant E. coli strain by more than ∼250-fold to 307.00 µg/g DCW via metabolic engineering and optimization of fermentation conditions. Beyond our scientific insights about the aerobic and anaerobic pathways and our demonstration of E. coli as a microbial biosynthetic platform for vitamin B12 production, our study offers an encouraging example of how the several dozen proteins of a complex biosynthetic pathway can be transferred between organisms to facilitate industrial production.

scholarly journals Cell-free biosynthesis of limonene using enzyme-enriched Escherichia coli lysates

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Quentin M Dudley ◽  
Connor J Nash ◽  
Michael C Jewett
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Enzymatic Synthesis ◽  
Biosynthetic Pathway ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Design Criteria ◽  
Acetyl Coa ◽  
E Coli ◽  
Enzymatic Pathways

Abstract Isoprenoids are an attractive class of metabolites for enzymatic synthesis from renewable substrates. However, metabolic engineering of microorganisms for monoterpenoid production is limited by the need for time-consuming, and often non-intuitive, combinatorial tuning of biosynthetic pathway variations to meet design criteria. Towards alleviating this limitation, the goal of this work was to build a modular, cell-free platform for construction and testing of monoterpenoid pathways, using the fragrance and flavoring molecule limonene as a model. In this platform, multiple Escherichia coli lysates, each enriched with a single overexpressed pathway enzyme, are mixed to construct the full biosynthetic pathway. First, we show the ability to synthesize limonene from six enriched lysates with mevalonate substrate, an adenosine triphosphate (ATP) source, and cofactors. Next, we extend the pathway to use glucose as a substrate, which relies on native metabolism in the extract to convert glucose to acetyl-CoA along with three additional enzymes to convert acetyl-CoA to mevalonate. We find that the native E. coli farnesyl diphosphate synthase (IspA) is active in the lysate and diverts flux from the pathway intermediate geranyl pyrophospahte to farnesyl pyrophsophate and the byproduct farnesol. By adjusting the relative levels of cofactors NAD+, ATP and CoA, the system can synthesize 0.66 mM (90.2 mg l−1) limonene over 24 h, a productivity of 3.8 mg l−1 h−1. Our results highlight the flexibility of crude lysates to sustain complex metabolism and, by activating a glucose-to-limonene pathway with 9 heterologous enzymes encompassing 20 biosynthetic steps, expands an approach of using enzyme-enriched lysates for constructing, characterizing and prototyping enzymatic pathways.

scholarly journals Systems Metabolic Engineering of Escherichia coli Improves Coconversion of Lignocellulose‐Derived Sugars

2019 ◽  
Vol 14 (9) ◽  
pp. 1800441 ◽  
Author(s):  
Joonhoon Kim ◽  
Mary Tremaine ◽  
Jeffrey A. Grass ◽  
Hugh M. Purdy ◽  
Robert Landick ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Systems Metabolic Engineering
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