The production of renewable chemicals is gaining attention over the past few years. The natural resources from which they can be derived in a sustainable way are most abundant in sugars, cellulose ...and hemicellulose. These highly functionalized molecules need to be de‐functionalized in order to be feedstocks for the chemical industry. A fundamentally different approach to chemistry thus becomes necessary, since the traditionally employed oil‐based chemicals normally lack functionality. This new chemical toolbox needs to be designed to guarantee the demands of future generations at a reasonable price. The surplus of functionality in sugars and glycerol consists of alcohol groups. To yield suitable renewable chemicals these natural products need to be defunctionalized by means of dehydroxylation. Here we review the possible approaches and evaluate them from a fundamental chemical aspect.
Glycerol and polyols from biomass need to be de‐functionalized in order to be a feedstock for the chemical industry. A fundamentally different approach to chemistry thus becomes necessary, since the traditionally employed oil‐based chemicals normally lack functionality. A new chemical toolbox needs to be designed to guarantee the demands of future generations.
Oleate hydratase catalyses the addition of water to the CC double bond of oleic acid to produce (
R
)-10-hydroxystearic acid. The enzyme requires an FAD cofactor that functions to optimise the active ...site structure. A wide range of unsaturated fatty acids can be hydrated at the C10 and in some cases the C13 position. The substrate scope can be expanded using ‘decoy’ small carboxylic acids to convert small chain alkenes to secondary alcohols, albeit at low conversion rates. Systematic protein engineering and directed evolution to widen the substrate scope and increase the conversion rate is possible, supported by new high throughput screening assays that have been developed. Multi-enzyme cascades allow the formation of a wide range of products including keto-fatty acids, secondary alcohols, secondary amines and α,ω-dicarboxylic acids.
Key points
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Phylogenetically distinct oleate hydratases may exhibit mechanistic differences.
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Protein engineering to improve productivity and substrate scope is possible.
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Multi-enzymatic cascades greatly widen the product portfolio.
The selective addition of water Resch, Verena; Hanefeld, Ulf
Catalysis science & technology,
2015, Letnik:
5, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Water is omnipresent and essential. Yet at the same time it is a rather unreactive molecule. The direct addition of water to C&z.dbd;C double bonds is therefore a challenge not answered convincingly. ...In this perspective we critically evaluate the selectivity and the applicability of the different catalytic approaches for water addition reactions: homogeneous, heterogeneous and bio-catalytic. Here we would like to discuss how to speed up water addition and even make it selective.
Water is omnipresent and unreactive. How to speed up water addition and even make it selective are highlighted in this perspective.
Water is the liquid of life. Nature has therefore evolved countless enzymes that catalyse the addition of water to C=C bonds, isolated or conjugated. These reactions are regio- and enantioselective, ...they are part of primary metabolism as well as the secondary metabolism. The enzymes that catalyse these reactions (hydratases or hydro-lyases) are applied industrially in selected cases. However, they are not generally used in the laboratory although they outperform all currently available catalytic chemical methodologies. This feature article highlights the potential that hydratases have for chemistry compared to the acid catalysed addition of water.
The enzymatic synthesis of esters and peptides is unfavoured in aqueous solvent systems due to competing hydrolysis. This can be overcome by using energy rich substrate analogues: elimination of a ...good leaving group temporarily establishes more favourable equilibrium conditions, allowing for (nearly) complete conversion. While kinetically controlled syntheses of esters and peptides in water are common knowledge in biocatalysis textbooks, the prevalence of kinetic control is less well known for other enzyme classes. Here, the general concepts of thermodynamic and kinetic control are illustrated at the example of the well‐studied synthesis of β‐lactam antibiotics and are shown to similarly also apply to other enzyme classes. Notably, the enzymatic synthesis of diastereomers shows the same characteristic energy profile as that of Diels‐Alder reactions. This allows for the selective synthesis of different diastereomers under either thermodynamically or kinetically controlled conditions. Prospects and pitfalls of this notion are discussed at the example of the thermodynamic epimerisation of hydroxysteroids and recent examples of kinetically controlled aldol reactions. Kinetic reaction control can therefore not only be used to increase conversions towards a single product, but also to selectively afford different diastereomers. This review highlights the prevalence of both concepts within the field of biocatalysis.
Biocatalysis: Kinetic control usually is applied in biocatalysis to improve product yields under thermodynamically challenging conditions, and the use of substrate analogues then allows for (near) complete conversion. The enzymatic synthesis of diastereomers shows an energy diagram similar to that of Diels‐Alder reactions and the same concepts of thermodynamic and kinetic control also apply to enzyme catalysis.
The hydrolase-catalyzed esterification of alcohols is the best established enzymatic transformation in today's organic chemistry, along with the corresponding ester hydrolysis. Over the years, ...various different acyl donors have been proposed to overcome the major limitation of the condensation of an alcohol and an acid, the unfavourable equilibrium. This review aims at screening the actual number of applications of the different acyl donors, and at assessing the "greenness" (or lack thereof) of the most applied among them. Indeed, the use of an enzyme to catalyze an esterification is often regarded as sufficient to define the whole transformation as "green". However, this definition can easily be misinterpreted if the contribution of the acyl donor to the overall process is overlooked, as is often the case. Aiming at filling this gap, this contribution evaluates the advantages and disadvantages of the acyl donors, and assesses their green credentials using an efficient tool in strategic planning, a strengths-weaknesses-opportunities-threats (SWOT) analysis. A calculation of the atom economy and E-factor for representative acylations involving each donor is included, as well as an analysis of the adherence of each process to the twelve principles of Green Chemistry.
The application of purified enzymes as well as whole-cell biocatalysts in synthetic organic chemistry is becoming more and more popular, and both academia and industry are keen on finding and ...developing novel enzymes capable of performing otherwise impossible or challenging reactions. The diverse genus
offers a multitude of promising enzymes, which therefore makes it one of the key bacterial hosts in many areas of research. This review focused on the broad utilization potential of the genus
in organic chemistry, thereby particularly highlighting the specific enzyme classes exploited and the reactions they catalyze. Additionally, close attention was paid to the substrate scope that each enzyme class covers. Overall, a comprehensive overview of the applicability of the genus
is provided, which puts this versatile microorganism in the spotlight of further research.
Enzymes are nature's catalyst of choice for the highly selective and efficient coupling of carbohydrates. Enzymatic sugar coupling is a competitive technology for industrial glycosylation reactions, ...since chemical synthetic routes require extensive use of laborious protection group manipulations and often lack regio- and stereoselectivity. The application of Leloir glycosyltransferases has received considerable attention in recent years and offers excellent control over the reactivity and selectivity of glycosylation reactions with unprotected carbohydrates, paving the way for previously inaccessible synthetic routes. The development of nucleotide recycling cascades has allowed for the efficient production and reuse of nucleotide sugar donors in robust one-pot multi-enzyme glycosylation cascades. In this way, large glycans and glycoconjugates with complex stereochemistry can be constructed. With recent advances, LeLoir glycosyltransferases are close to being applied industrially in multi-enzyme, programmable cascade glycosylations.
The synthetic properties of the Thiamine diphosphate (ThDP)-dependent pyruvate dehydrogenase E1 subunit from
(
PDH E1) was assessed for carboligation reactions with aliphatic ketoacids. Due to its ...role in metabolism,
PDH E1 was previously characterised with respect to its biochemical properties, but it was never applied for synthetic purposes. Here, we show that
PDH E1 is a promising biocatalyst for the production of chiral α-hydroxyketones. WT
PDH E1 shows a 180-250-fold higher catalytic efficiency towards 2-oxobutyrate or pyruvate, respectively, in comparison to engineered transketolase variants from
(TK
). Its broad active site cleft allows for the efficient conversion of both (
)- and (
)-configured α-hydroxyaldehydes, next to linear and branched aliphatic aldehydes as acceptor substrates under kinetically controlled conditions. The alternate, thermodynamically controlled self-reaction of aliphatic aldehydes was shown to be limited to low levels of conversion, which we propose to be due to their large hydration constants. Additionally, the thermodynamically controlled approach was demonstrated to suffer from a loss of stereoselectivity, which makes it unfeasible for aliphatic substrates.
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