Fructose 1,6-Bisphosphate Aldolase fromStaphylococcus carnosus: Overexpression, Structure Prediction, Stereoselectivity, and Application in the Synthesis of Bicyclic Sugars

The Transaldolase Family: New Synthetic Opportunities from an Ancient Enzyme Scaffold

“…Conversely, the bacterial class I FruA from Staphylococcus carnosus is a monomer (33 kDa). This enzyme has high pH and temperature stability,25, 53 making it particularly valuable for demanding synthetic applications 77…”

“…This is quite remarkable for three reasons: 1) such substrate combinations are challenging for aldolases, particularly for transaldolase descendants designed by nature for conversion of highly polar phosphorylated and polyhydroxylated substrates, because more generic structures with rather low oxygenation levels possess decreased aldol acceptor electrophilicities and lack opportunities for hydrogen bonding other than to aldehyde carbonyl, 2) these are the first examples of noncarbohydrate products with this low‐level substitution pattern produced by an aldolase,6, 7, 9, 14, 19 and 3) aliphatic α′,β′‐dihydroxylated alkylketones with strictly defined absolute and relative syn configurations are currently not accessible with similar efficiency by enantioselective chemical catalysis 4. For comparison, the diastereoselectivity of DHAP addition to propanal with FruA catalysis amounts to only 96 % de 77. 98 Similar nonpolar acceptors such as 2‐phenylethanal or 2‐benzyloxyethanal were also shown to be good substrates of FSA 86.…”

“…Enantioselectivity with 2‐hydroxyaldehydes: The hallmark of enzyme catalysis is the kinetic differentiation of chiral substrates, utilized for the preparation of, for example, enantiomerically pure building blocks by racemate resolution. However, enantioselectivity towards chiral aldehyde substrates in aldolases is often less frequently observed 77. 98, 102, 103 Notable exceptions are class II‐type aldolases,72, 104, 105 in which potential participation of the catalytic Lewis acid (usually Zn 2+ ) for binding of 2‐hydroxylated aldehydes has been discussed 70.…”

“…98, 102, 103 Notable exceptions are class II‐type aldolases,72, 104, 105 in which potential participation of the catalytic Lewis acid (usually Zn 2+ ) for binding of 2‐hydroxylated aldehydes has been discussed 70. 71 Effective discrimination of chiral aldehydes is mostly observed only with substrates carrying an extra charge: with FruA for Ga3P and analogues, for example 77. 102, 103…”

Short Enzymatic Synthesis ofL-Fucose Analogs

“…has been demonstrated that removal of this methyl group, Our synthetic approach was based on a two-step enzymatic sequence (Scheme 2), consisting of a CϪC bond for- [ ] Part 14: Ref. [22] ming reaction catalyzed by a dihydroxyacetone phosphate [a] Technische Universität Darmstadt, Institut für Organische Che-(DHAP, 3) dependent aldolase to effect asymmetric chain mie, was synthesized by reaction of 1,1-dimethoxyacetone 11 [19] with methylmagnesium bromide and subsequent acid hydrolysis. [28] At first, dimethoxyethanal 7 was used as a building block to prepare the remaining components, which were obtained by addition of suitable alk(en/yn)yl Grignard reagents followed by cleavage of the dimethyl acetals 8.…”