Construction of synthetic regulatory networks in yeast

Blount, Benjamin A.; Weenink, Tim; Ellis, Tom

doi:10.1016/j.febslet.2012.01.053

Cited by 73 publications

(73 citation statements)

References 110 publications

(179 reference statements)

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“…The combination of these modules resulted in a complicated network (Elowitz and Leibler, 2000) and genetic switches (Gardner et al, 2000). Recently, Blount et al (2012a) reviewed the status of Yeast genetic circuits. The genetic circuits in S. cerevisiae are far behind the E. coli.…”

Section: Role Of Synthetic Biology In Yeast Metabolic Engineering Andmentioning

confidence: 99%

“…But the presence of fatty acid, like myristic acid, changes the conformation of FadR, reduces the affinity to DNA-binding sequences, and deregulates the expression of genes (Blount et al, 2012a). Teo and Chang (2014) incorporated several upstream activator elements which in turn detect copper and phosphate starvation, and then downstream gene will only be activated by the depletion of both fatty acid and copper or fatty acid and phosphate.…”

Section: Role Of Synthetic Biology In Yeast Metabolic Engineering Andmentioning

confidence: 99%

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Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

et al. 2017

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The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools' development and application should focus on unexplored non-conventional yeast species.

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Section: Role Of Synthetic Biology In Yeast Metabolic Engineering Andmentioning

confidence: 99%

Section: Role Of Synthetic Biology In Yeast Metabolic Engineering Andmentioning

confidence: 99%

Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

et al. 2017

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“…By way of comparison, TeseleGen estimates that direct DNA synthesis of the same 240 constructs would cost $540,000 at current prices. Although peer-reviewed data are not yet available to evaluate the TeseleGen claims, it is clear that these kinds of improvements in model-driven synthetic biology [other recent advances are reviewed in (Koeppl 2011) (Blount et al 2012), (Medema et al 2012) and (Shiue and Prather 2012)] will reduce the number of cycles of design, construction and analysis needed to engineer systems that meet performance goals.…”

Section: Progress Toward Design-driven Synthetic Biologymentioning

confidence: 99%

Design-driven, multi-use research agendas to enable applied synthetic biology for global health

Carothers

2013

Syst Synth Biol

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Many of the synthetic biological devices, pathways and systems that can be engineered are multi-use, in the sense that they could be used both for commerciallyimportant applications and to help meet global health needs. The on-going development of models and simulation tools for assembling component parts into functionally-complex devices and systems will enable successful engineering with much less trial-and-error experimentation and laboratory infrastructure. As illustrations, I draw upon recent examples from my own work and the broader Keasling research group at the University of California Berkeley and the Joint BioEnergy Institute, of which I was formerly a part. By combining multi-use synthetic biology research agendas with advanced computer-aided design tool creation, it may be possible to more rapidly engineer safe and effective synthetic biology technologies that help address a wide range of global health problems.

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“…Most popular are the GAL promoters and the heterologous doxycycline responsive Tet promoters (Blount et al, 2012). These systems are inherently limited by the requirement for the addition of expensive inducers to the media, and in the case of the GAL promoters by the repression of gene expression on glucose.…”

Section: Introductionmentioning

confidence: 99%

Engineering yeast shikimate pathway towards production of aromatics: rational design of a chassis cell using systems and synthetic biology

Averesch¹

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Aromatic building blocks are amongst the most important bulk feedstocks in the chemical industry. As these compounds are commonly derived from petrochemistry, obtaining them is becoming more and more a matter of costs and sustainability. Biochemistry gives rise to a wealth of compounds that can potentially replace current petroleum-based chemicals or be used for novel materials. The aromatic compounds para-aminobenzoic acid (pABA) and para-hydroxybenzoic acid (pHBA) and the aromatics derived compound cis,cismuconic acid (ccMA) can be precursors for, but are not limited to, terephthalic or/and adipic acid. These are essential feedstocks for the production of PET and nylon. The three compounds can be derived from the shikimate pathway, an anabolic pathway leading to the biosynthesis of aromatic amino acids, present in certain prokaryotes and eukaryotes, including fungi. By combination of metabolic modelling with genetic engineering, a microbial production system based on the yeast Saccharomyces cerevisiae can be designed, which effectively channels flux into the target compounds.In order to develop a competitive bio-based process, yields, titers and rates need to be maximized. While productivity or rates in a process can be altered using genetic engineering, carbon yield, and pathway feasibility are stoichiometrically and thermodynamically predetermined. Both limitations need to be considered when designing a microbial production system. For formation of adipic acid and precursors many bio-based routes exists. More rational than just picking one for in vivo studies rather all available biochemical pathways were examined in silico using metabolic modelling. To compare theoretical yields and reaction thermodynamics an interface that allowed network-embedded thermodynamic analysis of elementary flux modes was developed. This allowed distinguishing between thermodynamically feasible and infeasible flux distributions. Feasible maximum theoretical product carbon yields were substantially different in E. coli and S. cerevisiae metabolic models and ranged from 32% to 92%. Further, many pathways appeared to be restricted by a thermodynamic equilibrium lying on the substrate side, some even infeasible.The only routes that deliver significant product yields and were thermodynamically favoured were shikimate pathway based. Being currently of strong scientific interest, recent implementations of these pathways in E. coli and S. cerevisiae were evaluated and strain construction strategies optimized, using the concept of constrained minimal cut-sets.Especially in S. cerevisiae a single non-obvious knock-out target allowed coupling of growth to product formation; in particular, the deletion of the pyruvate kinase reaction resulted in a minimum yield constraint of 28%.Though unique to shikimate pathway, this strategy is transferrable to other products which are derived from chorismate and also involve the formation of pyruvate as a by-product. This applies to pHBA. With further optimizations, the strategy was applied in...

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Construction of synthetic regulatory networks in yeast

Cited by 73 publications

References 110 publications

Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

Design-driven, multi-use research agendas to enable applied synthetic biology for global health

Engineering yeast shikimate pathway towards production of aromatics: rational design of a chassis cell using systems and synthetic biology

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