Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• Abstract Thiamin diphosphate (ThDP)-dependent enzymes constitute a large class of enzymes that catalyze a diverse range of reactions. Many are involved in stereospecific carbon–carbon bond formation and, consequently, have found increasing interest and utility as chiral catalysts in various biocatalytic

• , serves as the prototypical ThDP-dependent enzyme. A model of the active site was constructed on the basis of available crystal structures, and the cofactor states were characterized in the presence of three different ligands (crystallographic water, benzoylformate as substrate, and (R)-mandelate as

• catalytically inactive tricyclic state. Conversely, the inhibitor binding greatly destabilized the ylide formation. Together, these observations have significant implications for the reaction kinetics of the ThDP-dependent enzymes, and, potentially, for the use of unnatural substrates in such reactions

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• asymmetric version of acyloin-type reactions was also investigated in our laboratory operating packed-bed bioreactors functionalized with a suitable thiamine diphosphate (ThDP)-dependent enzyme supported on mesoporous silica [17]. Overall, the so far reported umpolung flow processes [12][13][14][15][16][17

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• very strong inhibitor, with a Ki value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes. Keywords: furan synthesis; gold-catalysed cyclisation

• ., pyruvate dehydrogenase, pyruvate decarboxylase), the formation of amino acid precursors (acetohydroxy acid synthase), and ketol transfer between sugars (transketolase) [1]. One common feature of ThDP-dependent enzymes is to catalyse the cleavage and formation of bonds adjacent to the carbon of a carbonyl

• group with the thiazolium ring of ThDP acting as an electron sink during catalysis in order to stabilise what would otherwise be an acyl carbanion in the form of an enamine intermediate [2]. The catalytic cycle for pyruvate decarboxylase (PDC, a representative ThDP-dependent enzyme), first proposed by

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• to be generated by the putative prephenate dehydrogenase NpR1269. Both substrates are then further transformed by the thiamin diphosphate (ThDP)-dependent enzyme NpR1276 to isomeric acyloins representing one-half of the carbon framework of scytonemin [71]. The enzyme showed a remarkable selectivity