Environmentally compatible synthesis of adipic acid from D-glucose

Draths, K. M.; Frost, J. W.

doi:10.1021/ja00080a057

Cited by 273 publications

(183 citation statements)

References 0 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…Production methods using renewable resources, such as lignocellulose, are potentially attractive, provided that they can be cost-effective. However, despite progress in microbial MA production, previous studies have suffered from low yields and titers and high accumulation of intermediate metabolites (17)(18)(19)(20)(21)(22). …”

mentioning

confidence: 99%

Engineering Escherichia coli coculture systems for the production of biochemical products

Zhang

Pereira

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

258

199

View full text Add to dashboard Cite

Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an Escherichia coli-E. coli coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical cis,cis-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. By efficiently producing another compound, 4-hydroxybenzoic acid, we also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.metabolic engineering | microbial coculture | muconic acid | 4-hydroxybenzoic acidM etabolic engineering and synthetic biology have made great strides in constructing and optimizing metabolic pathways for biochemical product synthesis in a pure culture (1, 2). There are, however, situations where this approach may be limited, as in the cases where (i) a single host cell cannot provide an optimal environment for the functioning of all pathway enzymes, (ii) biosynthetic efficiency is reduced due to overwhelming metabolic stress from the overexpression of long and complex pathways (3, 4), or (iii) pathway intermediates are secreted yielding undesired byproducts and reducing substrate utilization (5, 6). The above limitations can potentially be overcome through the use of rationally designed microbial coculture systems. Different from previous modular engineering approaches, such coculturebased systems completely modularize and segregate a biosynthetic pathway into two separate cells, each of which carries a portion of the pathway, and thus can be engineered independently to achieve optimal functioning of the combined pathway.The concept of microbial cocultures is not new. However, previous research on microbial consortia was primarily concerned with the study of mixed population stability and dynamic interactions (7-11), although a few recent studies have reported the engineering of microbial consortia for utilization of simple sugars to make small molecules of central carbon metabolism, such as ethanol and lactate (12, 13). Progress was made recently, when a full n-butanol pathway was expressed in two separate E. coli cells to achieve higher production (14) and when a bacterium-yeast coculture was used to address the difficulties of functional reconstitution of a pathway involving prokaryotic and eukaryotic enzymes in a consortium, and thus improved production of complex pharmaceutical molecules (15). Here, we expand the generality of the coculture engineering by demonstrating that microbial cocultures can also be engineered to overcome more universal challenges in metabolic engineering, including high-level intermediate secretion and low-efficiency s...

show abstract

mentioning

confidence: 99%

Engineering Escherichia coli coculture systems for the production of biochemical products

Zhang

Pereira

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

258

199

View full text Add to dashboard Cite

show abstract

“…De novo production of muconic acid from glucose via the shikimate pathway ( Figure 5) has been pioneered in E. coli (Draths & Frost, 1994). The optimized process showed high maximum titers (36.8 g/L) after 48 h and yields of 22% (mol/mol) (Niu et al, 2002).…”

Section: Bio-based Production Of Adipic Acid and Potential Precursorsmentioning

confidence: 99%

“…Six fundamentally different pathways featuring unique intermediates and enzymatic conversions were compiled from patents (Frost & Draths, 1996, Frost & Draths, 1997, Boussie et al, 2010, Raemakers-Franken et al, 2012 and scientific publications (Draths & Frost, 1994, Weber et al, 2012, Curran et al, 2013, Sun et al, 2013, Yu et al, 2014, Babu et al, 2015, Clomburg et al, 2015, Deng & Mao, 2015, Sengupta et al, 2015, Vardon et al, 2015. In total 16 different main routes for carbon-flow were considered.…”

Section: Biochemical Pathways To Adipic Acidmentioning

confidence: 99%

“…Exceptions are the early work of the Frost lab on muconic acid production from glucose in E. coli (Draths & Frost, 1994, Frost & Draths, 1997, Niu et al, 2002 and routes via salicylate and from lignin-derived species (Deng et al, 2016) as well as the production of adipic acid with Thermobifida fusca (Deng & Mao, 2015). The higher muconic acid titers indicate the presence of some kind of active transport mechanism.…”

Section: Evaluation Of Different Scenarios For Product Exportmentioning

confidence: 99%

See 1 more Smart Citation

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

Averesch¹

View full text Add to dashboard Cite

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...

show abstract

“…26 We have already reported practical synthesis of adipic acid by the oxidation of cyclohexene with aqueous 30% H2O2 in the presence of small amounts of Na2WO4 and [CH3(n-C8H17)3N]HSO4 as a PTC.7d In our continuous work on the tungsten-catalyzed oxidation with H2O2, we have also developed the oxidation of cyclohexanone and cyclohexanol with aqueous 30% H2O2 by using H2W04 as a catalyst without PTC (Scheme 2). lysts is that they can be readily separated using an external magnet, which achieves simple separation of the catalysts without filtration.…”

mentioning

confidence: 99%