Journal ArticleDOI
Engineering dynamic pathway regulation using stress-response promoters
Robert H. Dahl,Fuzhong Zhang,Jorge Alonso-Gutierrez,Jorge Alonso-Gutierrez,Edward E. K. Baidoo,Edward E. K. Baidoo,Tanveer S. Batth,Tanveer S. Batth,Alyssa M. Redding-Johanson,Alyssa M. Redding-Johanson,Christopher J. Petzold,Christopher J. Petzold,Aindrila Mukhopadhyay,Aindrila Mukhopadhyay,Taek Soon Lee,Taek Soon Lee,Paul D. Adams,Paul D. Adams,Paul D. Adams,Jay D. Keasling +19 more
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TLDR
This paper applied whole-genome transcript arrays to identify promoters that respond to the accumulation of toxic intermediates, and then used these promoters to control accumulation of the intermediate and improve the final titers of a desired product.Abstract:
Heterologous pathways used in metabolic engineering may produce intermediates toxic to the cell. Dynamic control of pathway enzymes could prevent the accumulation of these metabolites, but such a strategy requires sensors, which are largely unknown, that can detect and respond to the metabolite. Here we applied whole-genome transcript arrays to identify promoters that respond to the accumulation of toxic intermediates, and then used these promoters to control accumulation of the intermediate and improve the final titers of a desired product. We apply this approach to regulate farnesyl pyrophosphate (FPP) production in the isoprenoid biosynthetic pathway in Escherichia coli. This strategy improved production of amorphadiene, the final product, by twofold over that from inducible or constitutive promoters, eliminated the need for expensive inducers, reduced acetate accumulation and improved growth. We extended this approach to another toxic intermediate to demonstrate the broad utility of identifying novel sensor-regulator systems for dynamic regulation.read more
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Journal ArticleDOI
The Applications of Promoter-gene-Engineered Biosensors.
TL;DR: This paper highlights the strategies of construction of promoter gene-engineered biosensors with human and bacteria genetic promoter arrays with regard to high-throughput screening (HTS) molecular drugs, the study of the membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factors, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer.
Journal ArticleDOI
Programming living sensors for environment, health and biomanufacturing.
TL;DR: In this article, the authors summarize the latest advances in synthetic biology and discuss how they could accelerate the development, enhance the performance and address the present limitations of microbial sensors to facilitate their use in the field.
Journal ArticleDOI
Recent advances in developing and applying biosensors for synthetic biology
TL;DR: In this review, recent innovations and advancements that have led to the generation of robust, reliable, and flexible biosensors for utility across basic biological research and synthetic biology tools, including biological engineering efforts and clinical applications are compiled.
Journal ArticleDOI
Engineering of cis-Element in Saccharomyces cerevisiae for Efficient Accumulation of Value-Added Compound Squalene via Downregulation of the Downstream Metabolic Flux.
TL;DR: In this paper, marO, a cis-element of Escherichia coli mar operator, was explored to engineer promoters of Saccharomyces cerevisiae for downregulation.
Dissertation
Improvement of D-glucaric acid production in Escherichia coli
TL;DR: Although the attempts to create robust, controllable genetic timers in this thesis were unsuccessful, these attempts provided significant insight into limitations currently preventing widespread application of synthetic biology devices to metabolic engineering problems.
References
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Journal ArticleDOI
Production of the antimalarial drug precursor artemisinic acid in engineered yeast
Dae-Kyun Ro,Eric M. Paradise,Mario Ouellet,Karl Fisher,Karyn L. Newman,John M. Ndungu,Ho Kimberly,Eachus Rachel,Timothy S. Ham,James Kirby,Michelle C. Y. Chang,Sydnor T. Withers,Yoichiro Shiba,Richmond Sarpong,Jay D. Keasling +14 more
TL;DR: The engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l-1) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase from A. annua that performs a three-step oxidation of amorpha-4,11-diene to art Artemisinic acid.
Journal ArticleDOI
Genesis: cluster analysis of microarray data
TL;DR: Genesis integrates various tools for microarray data analysis such as filters, normalization and visualization tools, distance measures as well as common clustering algorithms including hierarchical clustering, self-organizing maps, k-means, principal component analysis, and support vector machines.
Journal ArticleDOI
Engineering a mevalonate pathway in Escherichia coli for production of terpenoids
TL;DR: The strains developed in this study can serve as platform hosts for the production of any terpenoid compound for which a terpene synthase gene is available, and are the universal precursors to all isoprenoids.
Journal ArticleDOI
Automated design of synthetic ribosome binding sites to control protein expression
TL;DR: A predictive method for designing synthetic ribosome binding sites is developed, enabling a rational control over the protein expression level, and is demonstrated by rationally optimizing protein expression to connect a genetic sensor to a synthetic circuit.
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