C−C Bond-Forming Lyases in Organic Synthesis

Brovetto, Margarita; Gamenara, Daniela; Saenz‐Méndez, Patricia; Seoane, Gustavo

doi:10.1021/cr100299p

Cited by 212 publications

(126 citation statements)

References 679 publications

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“…In this regard, dihydroxyacetone phosphate (DHAP)-dependent aldolases found particular utility and many ingenious applications were developed using a diverse range of aldehyde acceptors. The subsequent identification of four stereocomplementary DHAP aldolases that provided each of the four possible diastereomeric aldol addition products allowed this technology to mature into a well-accepted synthetic methodology (for recent reviews, see Brovetto, Gamenara, Mendez, & Seoane, 2011;Clapes, Fessner, Sprenger, & Samland, 2010).…”

Section: Introductionmentioning

confidence: 99%

Threonine Aldolases

Franz¹,

Stewart²

2014

Advances in Applied Microbiology

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Section: Introductionmentioning

confidence: 99%

Threonine Aldolases

Franz¹,

Stewart²

2014

Advances in Applied Microbiology

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“…FucA, FruA, RhaD, and TagA generally form (3R,4R), (3S,4R), (3R,4S), and (3S,4S) stereoconfigurations, respectively (1,2). However, some aldolases sometimes lost their strict stereoselectivity at the C-4 stereocenter with some aldehydes as substrates.…”

Section: Dhap-dependent Aldolases Create Two New Stereogenic Centers mentioning

confidence: 99%

“…A ldolases are remarkably useful and have been widely investigated for catalyzed COC bond formation (1). The ability to catalyze aldol addition reactions from small chiral polyfunctional molecules and generate up to two new stereogenic centers allows aldolases to synthesize a broad range of both natural and novel polyhydroxylated compounds.…”

mentioning

confidence: 99%

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

Yang

Men

et al. 2015

Appl Environ Microbiol

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The property of loose stereochemical control at aldol products from aldolases helped to synthesize multiple polyhydroxylated compounds with nonnatural stereoconfiguration. In this study, we discovered for the first time that some fructose 1,6-diphosphate aldolases (FruA) and tagatose 1,6-diphosphate (TagA) aldolases lost their strict stereoselectivity when using L-glyceraldehyde and synthesized not only L-sorbose but also a high proportion of L-psicose. Among the aldolases tested, TagA A ldolases are remarkably useful and have been widely investigated for catalyzed COC bond formation (1). The ability to catalyze aldol addition reactions from small chiral polyfunctional molecules and generate up to two new stereogenic centers allows aldolases to synthesize a broad range of both natural and novel polyhydroxylated compounds. Among the aldolase families, dihydroxyacetone-phosphate (DHAP)-dependent aldolases, which utilize DHAP as the donor substrate and accept a broad range of acceptor aldehydes, are widely investigated. Well-known members of this class include fuculose 1-phosphate aldolase (FucA), rhamnulose 1-phosphate aldolase (RhaD), fructose 1,6-diphosphate aldolase (FruA), and tagatose 1,6-diphosphate aldolase (TagA) (2). These enzymes have been used to synthesize several new deoxy or phosphorylated sugars and iminocyclitols (3-5). DHAP-dependent aldolases create two new stereogenic centers at C atoms 3 and 4 ([3S,4R], [3S,4S], [3R,4S], [3R,4R]). FucA, FruA, RhaD, and TagA generally form (3R,4R), (3S,4R), (3R,4S), and (3S,4S) stereoconfigurations, respectively (1, 2). However, some aldolases sometimes lost their strict stereoselectivity at the C-4 stereocenter with some aldehydes as substrates. For example, RhaD aldolase from Escherichia coli catalyzed DHAP and L-glyceraldehyde to form L-fructose (3R,4S). However, D-sorbose (3R,4S) and D-psicose (3R,4R) were formed when using D-glyceraldehyde (6-8). Moreover, FucA aldolase from E. coli catalyzed DHAP and L-glyceraldehyde to form the single product L-tagatose (3R,4R). However, FucA from Thermus thermophilus HB8 generated L-tagatose (3R,4R) and L-fructose (3R,4S) simultaneously from the same substrates. This finding indicated that aldolases had a high level of stereocontrol at C-3; however, the configuration of the stereocenter at C-4 in some cases depended on the particular enzyme and acceptor structure. This aldolase property can be well utilized to synthesize various types of rare sugars. Thus far, no reports have shown this property for FruA aldolase. In addition, TagA aldolases form diastereomer mixtures of product, in which instead of the natural configuration (3S,4S), those of the configuration (3S,4R) predominated (Ͼ90%) (4).L-Sugars, which are one large group of rare sugars, often hold enormous potential for applications in the pharmaceutical industry (9-11). For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles (12, 1...

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“…[27] The superfamily of ThDP-dependent decarboxylases is the most intensively studied superfamily, because of the potential of decarboxylases to catalyze the formation of mixed carboligation products from a donor substrate and an acceptor substrate with high chemo-and stereoselectivity. [29] Two members of the decarboxylase superfamily, benzoylformate decarboxylase from Pseudomonas putida (PpBFD) and benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), were thoroughly characterized for carboligation of acetaldehyde and benzaldehyde, which resulted in four different a-hydroxy ketones (Scheme 2): acetoin and benzoin resulting from condensation of acetaldehyde and benzaldehyde, respectively, and the mixed carboligation products 2-hydroxypropiophenone (2-HPP, Scheme 3) from benzaldehyde as donor and acetaldehyde as acceptor, and 1-phenyl-1-hydroxypropan-2-one (phenylacetylcarbinol, PAC) from acetaldehyde as donor and benzaldehyde as acceptor. Because the carboligation products contain a chiral center, decarboxylases are not only expected to show substrate specificity but also stereoselectivity.…”

Section: Case Study 1: Engineering the Regioselectivity Of Cytochromementioning

confidence: 99%

Systematic Analysis of Large Enzyme Families: Identification of Specificity‐ and Selectivity‐Determining Hotspots

Pleiss

2014

ChemCatChem

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A general strategy is described that integrates data mining of enzyme families and molecular modeling of enzyme–substrate interactions to identify selectivity hotspots and to design focused variant libraries for changed regio‐ and stereoselectivity. This strategy is demonstrated for two case studies; the design of cytochrome P450 monooxygenases with improved regioselectivity and of thiamine diphosphate dependent enzymes with improved stereoselectivity. In both families, two selectivity hotspots are found in almost all sequences, and simple, generic rules are established to predict the effect of mutations at these positions on selectivity. The crucial role of the hotspot positions is validated for an increasing number of enzymes by designing variants with improved or switched selectivity.

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C−C Bond-Forming Lyases in Organic Synthesis

Cited by 212 publications

References 679 publications

Threonine Aldolases

Threonine Aldolases

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

Systematic Analysis of Large Enzyme Families: Identification of Specificity‐ and Selectivity‐Determining Hotspots

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