Combining Metabolic Engineering and Electrocatalysis: Application to the Production of Polyamides from Sugar

Suástegui, Miguel; Matthiesen, John E.; Carraher, Jack M.; Hernández, Nacú; Quiroz, Natalia Rodriguez; Okerlund, Adam; Cochran, Eric W.; Shao, Zengyi; Tessonnier, Jean‐Philippe

doi:10.1002/ange.201509653

Cited by 46 publications

(67 citation statements)

References 42 publications

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“…The group of Balskus combined a microorganism as a 'living' biocatalyst, which produces hydrogen gas, and a heterogeneous catalyst (Pt or Pd) for the reduction of electron-deficient C-C double bonds in minimal media at room temperature (15 examples, up to 92% yield, see also section 'Reaction engineering to facilitate combinations of catalytic steps') 32 . Recently, Suastegui et al 33 realized a one-pot, but sequential process for the production of 3-hexenedioic acid starting from glucose. They combined an engineered Saccharomyces cerevisiae whole-cell biocatalyst for the production of muconic acid (0.5 g l -1 ) with a subsequent electrochemical reduction at ambient temperature and pressure.…”

Section: Nature Catalysismentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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N ature has evolved highly efficient systems in the form of cascade reactions, which assemble the metabolic networks that support life (growth and survival). The basic principle of cascade reactions is also frequently used in biocatalysis, using enzymes in isolation, as well as in combination with chemocatalysts (see Fig. 1 and Box 1 for definition of terms) [1][2][3][4][5][6][7] . As there is no need for purification and isolation of intermediates, operating time, production costs and waste are reduced, and concomitantly, overall yields are improved. In addition, the problem of unstable or difficult to handle intermediates can be overcome, and reactivity as well as selectivity can be enhanced by avoiding unfavourable reaction equilibria through the cooperative effects of multiple catalysts 8 . Starting in the 1980s, the early examples of the combination of chemo-and biocatalysts were reported by the van Bekkum group, who pioneered the development of a process to make the sugar substitute d-mannitol from readily available d-glucose through the combination of a heterogeneous metal-catalysed hydrogenation and an enzyme-catalysed isomerization 9 . The first broadly applied technology for the combination of enzyme and metalcatalysts, which was the research subject of many academic groups as well as industry, emerged in the 1990s from the Williams group 10,11 and aimed to achieve higher yields than classical kinetic resolution of racemates, thus overcoming the limitation of a maximum yield of 50% in the latter case. A prominent example of work that developed this theme is the combination of lipase-catalysed kinetic resolution via acylation of secondary alcohols with Pd-or Rh-catalysed racemization via reversible transfer hydrogenation to achieve a dynamic kinetic resolution (DKR) [12][13][14] . This example was facilitated in part because lipases are active and stable in organic solvents. Later, for instance, Turner's group combined a monoamine oxidase-catalysed imine formation with a chemical reduction 15 to achieve the 100% theoretical yield through a deracemization process. In addition to the combination of metalcatalysis with enzymes, organocatalysis, electrochemistry and light-induced reaction couples have since then been studied extensively, going far beyond the scope of a DKR.The challenges to combining chemo-and biocatalysis in cascades (see Box 1 for definitions and Table 1) can be daunting, not least the requirement for the chemical step to occur in the presence of water, the preferred solvent for enzymes 3 . This Review therefore highlights recent examples of the combination of chemo-and biocatalysts in aqueous multistep syntheses, and looks at how to overcome limitations by, for example, design of appropriate reaction conditions, protein engineering and advanced reactor concepts. Furthermore, trends such as the integration of transition metalcatalysis into microorganisms and the introduction of novel chemistry into engineered enzymes are discussed, and a critical assessment of the impact of this research ...

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Section: Nature Catalysismentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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“…In our study, we demonstrated how biosensors could be used in laboratory strains with limited engineering to improve titers, which at their best still were far from being commercially relevant. Indeed, in diploid yeast, production of 559.3 mg/L CCM has been recently reported 24 , whereas an E. coli-E. coli co-cultivation study has reported the production of 2 g/L CCM 47 . Though tolerance to low-pH fermentations should make yeast an economically feasible chassis for bio-based production of dicarboxylic acids such as CCM, the CCM biosensor design based on BenM may need to be adjusted or evolved as production hosts become better and the product titers become higher.…”

Section: Discussionmentioning

confidence: 99%

“…CCM is an intermediate from aromatic compound catabolism and an important precursor for bioplastics. Moreover, CCM biosynthesis recently has been refactored in yeast, yet without any high-throughput screening option available 24,25 . Third, BenM has a well-characterized DNA-binding site (here termed BenO) and mode of action ( Fig.…”

Section: A Prokaryote Transcription Activator In Yeastmentioning

confidence: 99%

“…To test this, we selected CCM and naringenin, for which highest titers in shake-flask-cultivated haploid yeast of ~1 mM (141 mg/L) and 0.2 mM (54 mg/L), respectively, have recently been reported 25,41 . Also, these two products are of general interest to biotechnology, because CCM is a platform chemical for the production of several valuable consumer bioplastics 24 , and naringenin belongs to a class of secondary metabolites called flavonoids with nutritional and agricultural value 42 .…”

Section: In Vivo Application Of Lttr-based Biosensors In Yeastmentioning

confidence: 99%

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Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast

et al. 2016

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TitleEngineering prokaryotic transcriptional activators as metabolite biosensors in yeast io-based production of chemicals and fuels is an attractive avenue to reduce dependence on petroleum. For bio-based production, biocatalysts must often be genetically modified to increase production. However, the current efficiency of genomeengineering methods and parts prospecting allows for unprecedented genotype diversity that vastly outstrips our ability to screen for best cell performance 1,2 .To meet current demand, bioengineers have started to develop genetically encoded devices and systems that enable screening and selection of better-performing biocatalysts in higher throughput. Genetic devices including oscillators, amplifiers and recorders, which have been developed based on fine-tuned relationships between input and output signals, are promising tools for programming and controlling gene expression in living cells [3][4][5] . These devices sense extracellular or intracellular perturbations and actuate cellular decision-making processes akin to logic gates in electrical circuits. Hence, from a diverse set of inputs, molecular gating components such as RNA aptamers and allosterically regulated transcription factors have been engineered to control outputs for applications such as high-throughput screening, actuation on cellular metabolism and evolution-based selection of optimal cell performance [6][7][8] .A key component in many of the reported devices is a ligandinducible transcriptional regulator. Transcriptional regulators are straightforward and powerful components, with many uses in genetic designs. Owing to their modular structure, transcriptional regulators have proven to be versatile platforms for genetically encoded Boolean logic functions 9,10 . In particular, gene switches based on ligand-binding transcriptional repressors bind to genomic targets in the absence of their cognate ligand and thereby repress gene expression of the downstream gene(s), whereas binding between ligand and repressor causes the release of the repressor from the DNA and thereby a derepression 11 . In such 'NOT' gates, simple steric hindrance of RNA polymerase progression, as in the case of the tetracycline-responsive gene switch TetR, have for decades been used for conditional control of gene expression in both prokaryotic and eukaryotic chassis 12,13 . Transcriptional repressors and other artificial transcriptional regulators can be further engineered, for example, via the addition of nuclear localization signals, destabilization domains and transcriptional activation regions, to repurpose conditional repressors into activators [13][14][15] . Though conceptually intriguing and practically relevant, the repurposing of logic gates can suffer from the inherent need for extensive engineering 9,16,17 .Though most ligand-inducible genetic devices adopted for eukaryotes historically have been founded on transcriptional repressors, a hitherto untapped resource for use in genetic designs is ligand-inducible transcriptional activators. Bac...

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“…15 A base solution containing ccMA and AA (internal standard) was prepared in D2O; separate solutions of HClO4, NaOH, and NaClO4 were prepared in D2O. Aliquots of each solution were added to J.…”

Section: Methodsmentioning

confidence: 99%

cis,cis-Muconic acid isomerization and catalytic conversion to biobased cyclic-C₆-1,4-diacid monomers

et al. 2017

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Renewable terephthalic and 1,4-cyclohexanedicarboxylic acids can be produced from biomass via muconic acid using a combination of biological and chemical processes. In this conversion scheme, cis,cis-mucononic acid is first obtained by fermentation using either sugar or lignin monomers as a feedstock. The diunsaturated cis,cis-diacid is then isomerized to trans,trans-muconic acid, reacted with biobased ethylene through Diels-Alder cycloaddition, and further hydrogenated or dehydrogenated to yield the desired 100% renewable cyclic dicarboxylic acid. The isomerization of cis,cis-to trans,trans-muconic acid represents the main bottleneck in this process due to undesired side reactions that promote ring closing to form lactones. Therefore, new technologies for the selective isomerization of muconic acid are urgently needed. Here, we studied the corresponding reaction kinetics to elucidate the mechanisms involved in both the isomerization and cyclization reactions with the objective to identify conditions that favor the selective formation of trans,trans-muconic acid. We demonstrate that the reactivity of muconic acid in aqueous media strongly depends on pH. Under alkaline conditions, cis,cis-muconic acid is deprotonated to the corresponding muconate dianion. This species is stable for extended periods of time and does not isomerize. Conversely, cis,cis-muconic acid readily isomerizes to its cis,trans-isomer under acidic conditions. Prolonged heating further triggers the intramolecular cyclizations through reaction of the carboxylic acid and alkene functionalities. The formation of the muconolactone and its dilactone is kinetically favored over the isomerization to trans,trans-muconic acid over a broad range of conditions. However, strategies involving the chelation of the carboxylates with inorganic salts or their solvation using polar aprotic solvents were found to hamper the ring closing reactions and allow the isomerization to trans,trans-muconic acid to proceed with high selectivity (88%). The obtained compound was further reacted with ethylene and hydrogenated to 1,4-cyclohexanedicarboxylic acid, an important monomer for the polyester and polyamide industries. Disciplines Biochemical and Biomolecular Engineering | Catalysis and Reaction Engineering | Chemical EngineeringComments This is a manuscript of an article published as Carraher, Jack M., Toni Pfennig, Radhika G. Rao, Brent H. Shanks, and Jean-Philippe Tessonnier. "cis, cis-Muconic acid isomerization and catalytic conversion to biobased cyclic-C 6-1, 4-diacid monomers." Green Chemistry 19, no. 13 (2017) Renewable terephthalic and 1,4-cyclohexanedicarboxylic acids can be produced from biomass via muconic acid using a combination of biological and chemical processes. In this conversion scheme, cis,cis-mucononic acid is first obtained by fermentation using either sugar or lignin monomers as a feedstock. The diunsaturated cis,cis-diacid is then isomerized to trans,trans-muconic acid, reacted with biobased ethylene through Diels-Alder cycloaddition, an...

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Combining Metabolic Engineering and Electrocatalysis: Application to the Production of Polyamides from Sugar

Cited by 46 publications

References 42 publications

Opportunities and challenges for combining chemo- and biocatalysis

Opportunities and challenges for combining chemo- and biocatalysis

Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast

cis,cis-Muconic acid isomerization and catalytic conversion to biobased cyclic-C₆-1,4-diacid monomers

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Combining Metabolic Engineering and Electrocatalysis: Application to the Production of Polyamides from Sugar

Cited by 46 publications

References 42 publications

Opportunities and challenges for combining chemo- and biocatalysis

Opportunities and challenges for combining chemo- and biocatalysis

Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast

cis,cis-Muconic acid isomerization and catalytic conversion to biobased cyclic-C6-1,4-diacid monomers

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Product

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cis,cis-Muconic acid isomerization and catalytic conversion to biobased cyclic-C₆-1,4-diacid monomers