Optimization of a Multi-Product Microbial Cell Factory for Multiple Objectives – A Paradigm for Metabolic Pathway Recipe

2017 ◽  
pp. 417-445
Author(s):  
Fook Choon Lee ◽  
Gade Pandu Rangaiah ◽  
Dong-Yup Lee
Keyword(s):  
Metabolic Pathway ◽  
Multiple Objectives ◽  
Microbial Cell ◽  
Cell Factory ◽  
Microbial Cell Factory

scholarly journals Metabolic engineering of Escherichia coli for de novo production of 3-phenylpropanol via retrobiosynthesis approach

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenning Liu ◽  
Xue Zhang ◽  
Dengwei Lei ◽  
Bin Qiao ◽  
Guang-Rong Zhao
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
De Novo ◽  
Microbial Cell ◽  
Cell Factory ◽  
Phosphopantetheinyl Transferase ◽  
Chromosome Engineering ◽  
Microbial Cell Factory ◽  
E Coli ◽  
Artificial Pathway

Abstract Background 3-Phenylpropanol with a pleasant odor is widely used in foods, beverages and cosmetics as a fragrance ingredient. It also acts as the precursor and reactant in pharmaceutical and chemical industries. Currently, petroleum-based manufacturing processes of 3-phenypropanol is environmentally unfriendly and unsustainable. In this study, we aim to engineer Escherichia coli as microbial cell factory for de novo production of 3-phenypropanol via retrobiosynthesis approach. Results Aided by in silico retrobiosynthesis analysis, we designed a novel 3-phenylpropanol biosynthetic pathway extending from l-phenylalanine and comprising the phenylalanine ammonia lyase (PAL), enoate reductase (ER), aryl carboxylic acid reductase (CAR) and phosphopantetheinyl transferase (PPTase). We screened the enzymes from plants and microorganisms and reconstructed the artificial pathway for conversion of 3-phenylpropanol from l-phenylalanine. Then we conducted chromosome engineering to increase the supply of precursor l-phenylalanine and combined the upstream l-phenylalanine pathway and downstream 3-phenylpropanol pathway. Finally, we regulated the metabolic pathway strength and optimized fermentation conditions. As a consequence, metabolically engineered E. coli strain produced 847.97 mg/L of 3-phenypropanol at 24 h using glucose-glycerol mixture as co-carbon source. Conclusions We successfully developed an artificial 3-phenylpropanol pathway based on retrobiosynthesis approach, and highest titer of 3-phenylpropanol was achieved in E. coli via systems metabolic engineering strategies including enzyme sources variety, chromosome engineering, metabolic strength balancing and fermentation optimization. This work provides an engineered strain with industrial potential for production of 3-phenylpropanol, and the strategies applied here could be practical for bioengineers to design and reconstruct the microbial cell factory for high valuable chemicals.

Soil: Microbial Cell Factory for Assortment with Beneficial Role in Agriculture

2019 ◽  
pp. 63-92 ◽  
Author(s):  
Pratiksha Singh ◽  
Rajesh Kumar Singh ◽  
Mohini Prabha Singh ◽  
Qi Qi Song ◽  
Manoj K. Solanki ◽  
...  
Keyword(s):  
Microbial Cell ◽  
Cell Factory ◽  
Microbial Cell Factory ◽  
Soil Microbial ◽  
Beneficial Role

scholarly journals Intelligent microbial cell factory with genetic pH shooting (GPS) for cell self-responsive base/acid regulation

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Chenyi Li ◽  
Xiaopeng Gao ◽  
Xiao Peng ◽  
Jinlin Li ◽  
Wenxin Bai ◽  
...  
Keyword(s):  
Ph Regulation ◽  
Self Regulation ◽  
Scale Up ◽  
Microbial Cell ◽  
Production Costs ◽  
Cell Factory ◽  
Ph Sensing ◽  
Genetic Circuits ◽  
Microbial Cell Factory ◽  
Cell Factories

Abstract Background In industrial fermentation, pH fluctuation resulted from microbial metabolism influences the strain performance and the final production. The common way to control pH is adding acid or alkali after probe detection, which is not a fine-tuned method and often leads to increased costs and complex downstream processing. Here, we constructed an intelligent pH-sensing and controlling genetic circuits called “Genetic pH Shooting (GPS)” to realize microbial self-regulation of pH. Results In order to achieve the self-regulation of pH, GPS circuits consisting of pH-sensing promoters and acid-/alkali-producing genes were designed and constructed. Designed pH-sensing promoters in the GPS can respond to high or low pHs and generate acidic or alkaline substances, achieving endogenously self-responsive pH adjustments. Base shooting circuit (BSC) and acid shooting circuit (ASC) were constructed and enabled better cell growth under alkaline or acidic conditions, respectively. Furthermore, the genetic circuits including GPS, BSC and ASC were applied to lycopene production with a higher yield without an artificial pH regulation compared with the control under pH values ranging from 5.0 to 9.0. In scale-up fermentations, the lycopene titer in the engineered strain harboring GPS was increased by 137.3% and ammonia usage decreased by 35.6%. Conclusions The pH self-regulation achieved through the GPS circuits is helpful to construct intelligent microbial cell factories and reduce the production costs, which would be much useful in industrial applications.

ChemInform Abstract: The Microbial Cell Factory

ChemInform ◽  
2012 ◽  
Vol 43 (29) ◽  
pp. no-no
Author(s):  
Cormac D. Murphy
Keyword(s):  
Microbial Cell ◽  
Cell Factory ◽  
Microbial Cell Factory

Organic acids from lignocellulose: Candida lignohabitans as a new microbial cell factory

2015 ◽  
Vol 42 (5) ◽  
pp. 681-691 ◽  
Author(s):  
Martina Bellasio ◽  
Diethard Mattanovich ◽  
Michael Sauer ◽  
Hans Marx
Keyword(s):  
Organic Acids ◽  
Microbial Cell ◽  
Cell Factory ◽  
Microbial Cell Factory

scholarly journals Modular, synthetic chromosomes as new tools for large scale engineering of metabolism

2021 ◽  
Author(s):  
Eline Postma ◽  
Else-Jasmijn Hassing ◽  
Venda Mangkusaputra ◽  
Jordi Geelhoed ◽  
Pilar de la Torre ◽  
...  
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Metabolic Networks ◽  
De Novo ◽  
Microbial Cell ◽  
Cell Factory ◽  
Microbial Cell Factory ◽  
Microbial Cell Factories ◽  
Cell Factories

The construction of powerful cell factories requires intensive genetic engineering for the addition of new functionalities and the remodeling of native pathways and processes. The present study demonstrates the feasibility of extensive genome reprogramming using modular, specialized de novo-assembled neochromosomes in yeast. The in vivo assembly of linear and circular neochromosomes, carrying 20 native and 21 heterologous genes, enabled the first de novo production in a microbial cell factory of anthocyanins, plant compounds with a broad range pharmacological properties. Turned into exclusive expression platforms for heterologous and essential metabolic routes, the neochromosomes mimic native chromosomes regarding mitotic and genetic stability, copy number, harmlessness for the host and editability by CRISPR/Cas9. This study paves the way for future microbial cell factories with modular genomes in which core metabolic networks, localized on satellite, specialized neochromosomes can be swapped for alternative configurations and serve as landing pads for the addition of functionalities.

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