Formate dehydrogenase - a biocatalyst with novel applications in organic chemistry

Abstract

In the field of industrial biocatalysis, formate dehydrogenase (FDH) is well established, in particular for its broad application in cofactor regeneration. Further applications have been limited by the enzyme's narrow range of substrates. These restrictions have been overcome now by the finding, that the enzyme is capable of selectively cleaving formic acid esters to the respective alcohol. Five homologous alkyl formates and phenyl formate as an aromatic ester were converted quantitatively by FDH from Candida boidinii in a batch reaction within 3 to 5 h. The substrates were turned irreversibly into carbon dioxide and the respective alcohol through hydride abstraction from the formyl group with full conversion. The mechanism shows parallels to hydrolysis reactions of the A(AC)1-type. K(M)-values and reactions rates of the tested formic acid esters display a tendency to higher conversion rates with increasing chain length. FDH emerged to be a superior deformylation catalyst compared to hydrolases as well as classical catalysts, as was shown by the selective deformylation of 1-acetoxy-4-formoxy butane (92%) and 1,3-bis(3-formoxypropyl)tetramethyldisiloxane. In particular its capability to distinguish between formic acid esters and non-formic acid esters renders the method particularly suitable for protective group chemistry. Furthermore the completeness of deformylation allows for converting substrates highly incompatible with aqueous media like siloxanes within a few hours.

Lipase catalyzed esterification of formic acid in solvent and solvent-free systems

“…Butyl formate has a fruity, plum-like odor and corresponding taste and n-octyl formate has a fruity odor with a rose-orange note and a bitter flavor, refreshingly fruity green at low concentrations (Nurdock, 2010). Recently, formate esters such as octyl formate was used by formate dehydrogenase as a reactive solvent to regenerate NADH from NAD + (Frohlich et al, 2011;Janssen et al, 2014).…”

Microbial surface displaying formate dehydrogenase and its application in optical detection of formate

“…It was reported that organic solvents have effects on the enzyme activities [43,44]. The effects of organic solvents on the stability of cell-surface-displayed FDH were investigated (Table 3).…”

The Boundary Layer as Reaction Compartment for the Synthesis of Hydroxyalkyl-functionalized Siloxanes

“…methyl, ethyl and propyl ester, had proven successful, we tested this variant also for siloxane 2. Advantageously, potential contributions of hydrolase activity, in concert with FDH-mediated oxidation of intermediately released formic acid, were shown to not interfere with the FDH-mediated deformylation of 2 [19]. Likewise a potential backward reaction through oxidation of isopropanol formed in the course of cofactor regeneration had no effect on the reaction, since the FDHmediated hydrogenation of CO 2 to formic acid firstly is too slow within the time scale of this reaction, and secondly it requires pressure > 5 MPa to produce detectable amounts within 10 h.…”