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
Citations
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Journal ArticleDOI
Microbial Cell Factories for the Production of Terpenoid Flavor and Fragrance Compounds
TL;DR: The main part of this work focuses on key strategies and recent advances to engineer microbes to become efficient terpenoid producers.
Journal ArticleDOI
Synthetic Biology-The Synthesis of Biology.
TL;DR: The in vitro design, synthesis, and transfer of complete genomes into host cells point to the future of synthetic biology: the creation of designer cells with tailored desirable properties for biomedicine and biotechnology.
Journal ArticleDOI
Multivariate modular metabolic engineering for pathway and strain optimization.
Bradley W. Biggs,Brecht De Paepe,Christine Nicole S. Santos,Marjan De Mey,Parayil Kumaran Ajikumar +4 more
TL;DR: In this technique, key enzymes are organized into distinct modules and simultaneously varied based on expression to balance flux through a pathway, which has the potential to systematize and revolutionize the field of metabolic engineering and industrial biotechnology.
Journal ArticleDOI
Modular enzyme assembly for enhanced cascade biocatalysis and metabolic flux
Wei Kang,Tian Ma,Min Liu,Jiale Qu,Zhenjun Liu,Huawei Zhang,Bin Shi,Shuai Fu,Juncai Ma,Louis Tung Faat Lai,Sicong He,Jianan Y. Qu,Shannon Wing-Ngor Au,Byung-Ho Kang,Wilson Chun Yu Lau,Zixin Deng,Zixin Deng,Jiang Xia,Tiangang Liu +18 more
TL;DR: A pair of short peptide tags (RIAD and RIDD) are chosen to create scaffold-free enzyme assemblies and synthetic metabolic nodes to impose metabolic control in biosynthetic microbe factories.
Dynamic metabolic engineering: New strategies for developing responsive cell factories
TL;DR: This review highlights some of the recently published work related to dynamic metabolic engineering strategies and explores how advances in high‐throughput screening and synthetic biology can support development of new dynamic systems.
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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