Bio‐based production of C2–C6 platform chemicals

Jang, Yu‐Sin; Kim, Byoung-Jin; Shin, Jae Ho; Choi, Yong Jun; Choi, Sangdun; Song, Chul-Hwa; Lee, Joungmin; Park, Hye Gwon; Lee, Sang Yup

doi:10.1002/bit.24599

Cited by 348 publications

(214 citation statements)

References 193 publications

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“…Using metabolic engineering these capabilities are already being exploited to create new organisms that use abundant and renewable feedstocks to efficiently produce an expanding spectrum of valuable chemicals (Jang et al, 2012. In particular aromatics have great potential for bio-based production as the shikimate pathway gives rise to a wealth of aromatics and derived compounds, with diverse applications in different industries, including the chemical one (Hansen et al, 2009, Curran et al, 2013, Krömer et al, 2013, Jendresen et al, 2015, Rodriguez et al, 2015, Williams et al, 2015.…”

Section: Significance Of Bio-derived Aromatic Feedstocks For Chemicalmentioning

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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Section: Significance Of Bio-derived Aromatic Feedstocks For Chemicalmentioning

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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“…260,261 Sugar fermentations are dominating in bio-industry and were therefore investigated to determine the potential of electrical enhancement to boost these processes. 262 As a second substrate of interest glycerol was chosen as it represents a cheap C-source often produced as a waste in biodiesel production. 263 Its more reductive state compared to glucose suggests it could result in higher yields when converted into more reduced compounds and require less additional electrons.…”

Section: 259mentioning

confidence: 99%

“…264 A current review by JANG et al summarises important C 2 -C 6 -products and their biological production. 262 All anaerobic production pathways were implemented in the presented metabolic network and the theoretical yields of each compound under electrical enhancement were analysed. Figure 12 shows the metabolic fluxmap of the presented E. coli carbon network including all product pathways.…”

Section: 259mentioning

confidence: 99%

“…2,3-BDO has applications in the food, pharmaceuticals as well as agrochemical markets and is still produced from fossil fuel feedstocks. 262 But there are several promising approaches for its microbiological production from sugars or glycerol. 278 It is metabolically derived from pyruvate via acetolactate and the recent progress in process optimization suggests bio-2,3-BDO will hit the industrial market soon.…”

Section: 3-butanediol (23-bdo) Is An Interesting Example To Study mentioning

confidence: 99%

“…221 The main product is usually acetate but the central intermediate acetyl-CoA presents an excellent building block for various commodities. 165,262 Tools for genetic manipulation of acetogenic organisms are rapidly evolving, offering a fast growing set of techniques for pathway engineering.…”

Section: Acetogenic Organisms As Host For Mesmentioning

confidence: 99%

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Understanding extracellular electron transport of industrial microorganisms and optimization for production application

Kracke¹

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Microbial electrosynthesis (MES) and electro-fermentation are novel approaches to increase microbial production by stimulating the metabolism of the cells electrically. The technique is still in its infancy and while already hyped as promising method to convert CO 2 or cheap carbon sources and electrical energy into valuable chemicals and fuels, little is known about its true potential. This project uses a combination of in silico and in vivo approaches to gather novel information about the benefits and limitations of microbial electrosynthesis as well as its fundamental mechanisms.Understanding microbial electron transport mechanisms is the key to optimization of any bioelectrochemical technology. Therefore, this work analyses the different electron transport chains that nature offers for organisms such as metal respiring bacteria and acetogens, but also standard biotechnological organisms currently used in bioproduction.Special focus lies on the essential connection of redox and energy metabolism, which is often ignored when studying bioelectrochemical systems. The possibility of extracellular electron exchange at different points in each organism is discussed regarding required redox potentials and effect on cellular redox and energy levels. Key compounds such as electron carriers (e.g. cytochromes, ferredoxins, quinones, flavins) are identified and analysed regarding their possible role in electrode-microbe-interactions.Based on these findings a stoichiometric network analysis is performed analysing the effect of electrical stimulation on the microbial metabolism theoretically. Escherichia coli is used as model organism for production with the aim to identify target processes for MES.For the first time, 20 different valuable products were screened for their potential to show increased yields during anaerobic electrically enhanced fermentation. Surprisingly it was found that an increase in product formation by electrical enhancement is not necessarily dependent on the degree of reduction of the product but rather the metabolic pathway it is derived from. Contrary to the usual assumption a reduced product would always require electron supply by a cathode this study shows that a complex metabolic analysis is needed to identify the overall redox state of each process. A variety of beneficial processes is presented with product yield increases of maximal +36% in reductive and +84% in oxidative fermentations and final theoretical product yields up to 100%. This includes compounds that are already produced at industrial scale such as succinic acid, ii lysine and diaminopentane as well as potential novel bio-commodities such as isoprene, para-hydroxybenzoic acid and para-aminobenzoic acid. Furthermore, it is shown that the way of electron transport has major impact on achievable biomass and product yields. The coupling of electron transport to energy conservation could be identified as crucial for most processes.The in vivo approach of this project introduces the development of a standardised reactor platfor...

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Platform Molecules

Farmer

Mascal

2014

Introduction to Chemicals From Biomass

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Bio‐based production of C2–C6 platform chemicals

Cited by 348 publications

References 193 publications

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

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

Understanding extracellular electron transport of industrial microorganisms and optimization for production application

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