An Update on Developments in the Field of Thiamin Diphosphate-Dependent Enzymes

Jordan, Frank; Nemeria, Natalia S.; Balakrishnan, Anand; Chakraborty, Joydeep; Guevara, Elena; Nareddy, Pradeep; Patel, H.; Shim, Da Jeong; Wang, Junjie; Yang, Lisong; Zhang, Xu; Zhou, Jieyu

doi:10.1016/b978-0-12-409547-2.14833-4

Cited by 2 publications

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References 152 publications

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“…Formation of chiral products on an analytical scale by E. coli E1o was confirmed by recording the CD spectra of the products formed and by 1 H NMR spectroscopy (see Figure 4, panels A, B for chiral products identified) [69]. More recently, the studies were also extended at Rutgers to a carboligation-type synthesis using human E1o from 2-OG and from 2-OA [63,98]. With 2-OG as a substrate donor and glyoxylate as an acceptor, (R)-2-hydroxy-3-oxohexanedioic acid ((R)-2-hydroxy-3-oxoadipate) (Figure 4, panel A) was detected in the CD experiments with an estimated catalytic efficiency (k cat /K m,OG ) of about 4.8% compared to the E1o-specific activity (Figure 4, panel B).…”

Section: E Coli E1o Catalyzes the Formation Of Acetoin-like Products In A Carboligase Condensation Reactionmentioning

confidence: 98%

Engineering the 2-Oxoglutarate Dehydrogenase Complex to Understand Catalysis and Alter Substrate Recognition

et al. 2022

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The E. coli 2-oxoglutarate dehydrogenase complex (OGDHc) is a multienzyme complex in the tricarboxylic acid cycle, consisting of multiple copies of three components, 2-oxoglutarate dehydrogenase (E1o), dihydrolipoamide succinyltransferase (E2o) and dihydrolipoamide dehydrogenase (E3), which catalyze the formation of succinyl-CoA and NADH (+H+) from 2-oxoglutarate. This review summarizes applications of the site saturation mutagenesis (SSM) to engineer E. coli OGDHc with mechanistic and chemoenzymatic synthetic goals. First, E1o was engineered by creating SSM libraries at positions His260 and His298.Variants were identified that: (a) lead to acceptance of substrate analogues lacking the 5-carboxyl group and (b) performed carboligation reactions producing acetoin-like compounds with good enantioselectivity. Engineering the E2o catalytic (core) domain enabled (a) assignment of roles for pivotal residues involved in catalysis, (b) re-construction of the substrate-binding pocket to accept substrates other than succinyllysyldihydrolipoamide and (c) elucidation of the mechanism of trans-thioesterification to involve stabilization of a tetrahedral oxyanionic intermediate with hydrogen bonds by His375 and Asp374, rather than general acid–base catalysis which has been misunderstood for decades. The E. coli OGDHc is the first example of a 2-oxo acid dehydrogenase complex which was evolved to a 2-oxo aliphatic acid dehydrogenase complex by engineering two consecutive E1o and E2o components.

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Section: E Coli E1o Catalyzes the Formation Of Acetoin-like Products In A Carboligase Condensation Reactionmentioning

confidence: 98%

Engineering the 2-Oxoglutarate Dehydrogenase Complex to Understand Catalysis and Alter Substrate Recognition

et al. 2022

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“…TPP is a cofactor for many C−C bond making and breaking enzymatic reactions. 60 Based on the enhanced C( 2)-H acidity of the key thiazolium moiety of TPP, Breslow proposed a mechanism involving an initial deprotonation step to an NHC followed by reaction with the substrate via an enaminol-type intermediate (Scheme 12). 61 Subsequent screening of a broad range of related heterocyclic azolium catalysts demonstrated that 1,2,4triazolium salts were generally the most active and stereoselective of the range of N-heterocycles explored as independent organocatalysts (Scheme 13).…”

Section: ■ Thiamine Pyrophosphatementioning

confidence: 99%

“…Perhaps one of the most well-known cofactors among chemists is thiamine pyrophosphate (TPP) owing to its pivotal role in the development of N-heterocyclic carbene (NHC) organocatalysis. TPP is a cofactor for many C–C bond making and breaking enzymatic reactions . Based on the enhanced C (2)-H acidity of the key thiazolium moiety of TPP, Breslow proposed a mechanism involving an initial deprotonation step to an NHC followed by reaction with the substrate via an enaminol-type intermediate (Scheme ).…”

Section: Thiamine Pyrophosphatementioning

confidence: 99%

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Going Full Circle with Organocatalysis and Biocatalysis: The Latent Potential of Cofactor Mimics in Asymmetric Synthesis

2023

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Many enzymes work in tandem with small molecule cofactors, which have inspired organocatalyst designs. Chemical modification of cofactor scaffolds has increased organocatalytic reactivity and reaction scope. This synopsis presents a selection of recent advances in the use of cofactors (native and mimics) in organocatalysis and biocatalysis. We aim to highlight the benefits of combining fundamental knowledge gained in both bio- and organo-catalysis for asymmetric biocatalysis.

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An Update on Developments in the Field of Thiamin Diphosphate-Dependent Enzymes

Cited by 2 publications

References 152 publications

Engineering the 2-Oxoglutarate Dehydrogenase Complex to Understand Catalysis and Alter Substrate Recognition

Engineering the 2-Oxoglutarate Dehydrogenase Complex to Understand Catalysis and Alter Substrate Recognition

Going Full Circle with Organocatalysis and Biocatalysis: The Latent Potential of Cofactor Mimics in Asymmetric Synthesis

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