Non-Conventional Yeasts as Sources of Ene-Reductases for the Bioreduction of Chalcones

Abstract

Thirteen Non-Conventional Yeasts (NCYs) have been investigated for their ability to reduce activated C=C bonds of chalcones to obtain the corresponding dihydrochalcones. A possible correlation between bioreducing capacity of the NCYs and the substrate structure was estimated. Generally, whole-cells of the NCYs were able to hydrogenate the C=C double bond occurring in (E)-1,3-diphenylprop-2-en-1-one, while worthy bioconversion yields were obtained when the substrate exhibited the presence of a deactivating electron-withdrawing Cl substituent on the B-ring. On the contrary, no conversion was generally found, with a few exceptions, in the presence of an activating electron-donating substituent OH. The bioreduction aptitude of the NCYs was apparently correlated to the logP value: Compounds characterized by a higher logP exhibited a superior aptitude to be reduced by the NCYs than compounds with a lower logP value.

“A Study in Yellow”: Investigations in the Stereoselectivity of Ene‐Reductases

“…[49] In some cases, the driving force in the discovery of new ERs has been the need of new strategies for the synthesis of specific bioactive compounds: the interest for the bioreduction of chalcones lead to the identification of a new OYE homolog in the anaerobic gut bacterium Eubacterium ramulus [50] and, more recently, has highlighted the possibility of discovering new OYEs homologues in non-conventional yeasts. [51] Lastly, in an attempt to identify new homologs active on particularly sterically hindered substrates, an extensive data mining study on drain metagenomic samples afforded seven novel OYE-like enzymes with activity also on bi-and tricyclic enones. [52] The constant need for new biocatalytic tools for C=C bioreductions lead also to the exploration and characterization of non-OYE-like ERs, where the typical FMN is absent (nicotinamide-dependent double bond reductases (DBRs)) [2,10,53] or where it is replaced by a deazaflavin (F 420 -dependent ene-reductases (FDRs)).…”

Ene‐Reductase: A Multifaceted Biocatalyst in Organic Synthesis

“…Chalcones (enones) and dihydrochalcones (C=C double bond reduced form of chalcones) are important class of compounds for production of artificial sweeteners in food industry. The Forti group reported that thirteen non‐conventional yeasts (NCYs) [43] have the ability to reduce the unsaturated double bond in chalcones (Scheme 1d) and among them, nine have shown a conversion over 94 %. Generally, the whole‐cell reduction methods lack chemoselectivity, but fortunately, these strains selectively reduced the olefin bond by leaving C=O bond untouched.…”

“… (a) Whole cell catalysed reduction of malononitrile derivative, [33] (b) Reduction of ( R )‐carvone using ene‐reductase from the cyanobacterium Nostoc sp . PCC 7120, [34] (c) Reduction of α , β ‐unsaturated γ ‐ketophosphonates using ene‐reductases from M. circinelloides , [42] (d) Reduction of chalcones to dihydrochalcones by NCYs [43] …”

“…PCC 7120, [34] (c) Reduction of α,β-unsaturated γ-ketophosphonates using ene-reductases from M. circinelloides, [42] (d) Reduction of chalcones to dihydrochalcones by NCYs. [43] reported several Rhodococcus rhodochrous and R. erythropolis strains for ene-reductase activity to reduce C=C bond of substrates, including activated ketones, aldehyde, imide and nitro-compounds. This report also revealed that whole cells of all Rhodococcus strains showed apparent (S)-selectivity towards ketoisophorone, [38] while other enzymes resulted in (R)-selectivity.…”

Biotransformation of Hydroxychalcones as a Method of Obtaining Novel and Unpredictable Products Using Whole Cells of Bacteria

“…So far, the best-known enzymes responsible for the reduction of the C=C bond belongs to the Old Yellow Enzyme (OYE) family. Ene-reductases are flavin-dependent oxidoreductases that require NAD(P)H as a cofactor to their activity [14][15][16]. The OYE substrates include activated alkenes with an electron withdrawing groups (EWGs) such as aldehyde, ketone, nitro, carboxylic acid and other functional moieties [17].…”