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
Systematic engineering of pentose phosphate pathway improves Escherichia coli succinate production.
Zaigao Tan,Jing Chen,Xueli Zhang +2 more
TL;DR: This study systematically engineered the PPP for improving the supply of reducing equivalents and thus succinate production and these PPP engineering strategies and conclusions can also be applicable to the production of other reducing equivalent-dependent biorenewables.
Posted ContentDOI
Design and analysis of a Proportional-Integral-Derivative controller with biological molecules
TL;DR: It is illustrated through computational and analytical treatments that the addition of proportional and derivative control improves performance, and practical biomolecular implementations of these control strategies are discussed.
Journal ArticleDOI
Engineering tunable biosensors for monitoring putrescine in Escherichia coli
TL;DR: This study provides a strategy for engineering synthetic biosensor circuit for monitoring and tuning the dynamics in sensing putrescine, which can be generally applicable for monitoring other chemicals through taking a similar approach in circuit design.
Journal ArticleDOI
Two-stage carbon distribution and cofactor generation for improving l-threonine production of Escherichia coli.
Jiaheng Liu,Huiling Li,Hui Xiong,Xie Xixian,Ning Chen,Guangrong Zhao,Qinggele Caiyin,Hongji Zhu,Jianjun Qiao +8 more
TL;DR: A metabolic modification strategy of two‐stage carbon distribution and cofactor generation was proposed to address the above challenges in E. coli THRD, an l‐threonine producing strain and had potential to be applied in the production of many other desired oxaloacetate derivatives, especially those involving cofactor reactions.
Journal ArticleDOI
Controlling and exploiting cell-to-cell variation in metabolic engineering.
Tiebin Wang,Mary J. Dunlop +1 more
TL;DR: The potential of controlling variation as a novel approach towards improving performance of engineered cells is suggested and recent developments on strategies that can be employed to diminish, accept, or even exploit cell-to-cell variation are discussed.
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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