Bridging the gap between systems biology and synthetic biology

Liu, Di; Hoynes-O’Connor, Allison; Zhang, Fuzhong

doi:10.3389/fmicb.2013.00211

Cited by 27 publications

(17 citation statements)

References 70 publications

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“…The sheer complexity of biology has also hindered development of its formal mathematics. Synthetic biology has started to bridge the gap between biology and engineering [17].…”

Section: Scientist As Engineer and Technologistmentioning

confidence: 99%

Education and training for industrial biotechnology and engineering biology

Delebecque¹,

Philp

2018

Eng. biol.

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“…The sheer complexity of biology has also hindered development of its formal mathematics. Synthetic biology has started to bridge the gap between biology and engineering [17].…”

Section: Scientist As Engineer and Technologistmentioning

confidence: 99%

Education and training for industrial biotechnology and engineering biology

Delebecque¹,

Philp

2018

Eng. biol.

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“…Many of the strategies for controlling metabolite dynamics focus on controlling enzyme concentration . The use of transcriptional dynamic metabolic control is a way to cause metabolite concentrations to change over the course of production by changing enzyme concentrations (Figure ).…”

Section: Metabolite Dynamicsmentioning

confidence: 99%

Engineering Microbial Metabolite Dynamics and Heterogeneity

Schmitz

Hartline

Zhang

2017

Biotechnology Journal

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As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains.

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“…The control of protein synthesis is a major asset that synthetic biology builds upon. Strategies to adjust the amounts of mRNA molecules consist of varying the transcription initiation rate or termination frequency, of modulating RNA stability 19 or active removal of mRNA 20 . At the same time gene expression needs to be switched at the transcriptional level 21,22 .…”

Section: Introductionmentioning

confidence: 99%

A Methylation-Directed, Synthetic Pap Switch Based on Self-Complementary Regulatory DNA in an All-E. Coli Cell-Free Expression System

Worst¹,

Kurt²,

Finkler³

et al. 2020

Preprint

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<p>Pyelonephritis-associated pili (pap) enable migration of the uropathogenic Escherichia coli strain (UPEC) through the urinary tract. UPEC can switch between a stable 'ON phase' where the corresponding pap genes are expressed and a stable 'OFF phase' where their transcription is repressed. Hereditary, alternate DNA methylation of only two GATC motives within the regulatory region stabilizes the respective phase over many generations. The underlying molecular mechanism is only partly understood. Previous investigations suggest that in vivo phase-variation stability results from cooperative action of the transcriptional regulators Lrp and PapI. Here, we use an E. coli cell-free expression system to study the function of pap regulatory region based on a specially designed, synthetic construct flanked by two reporter genes encoding fluorescent proteins for simple readout. Based on our observations we suggest that Lrp and the conformation of the self-complementary regulatory DNA play a strong role in the regulation of phase-variation. Our work not only contributes to better understand the phase variation mechanism, but it represents a successful start for engineering stable, hereditary and strong expression control based on methylation.</p>

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Bridging the gap between systems biology and synthetic biology

Cited by 27 publications

References 70 publications

Education and training for industrial biotechnology and engineering biology

Education and training for industrial biotechnology and engineering biology

Engineering Microbial Metabolite Dynamics and Heterogeneity

A Methylation-Directed, Synthetic Pap Switch Based on Self-Complementary Regulatory DNA in an All-E. Coli Cell-Free Expression System

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