Abstract:Birch reductions of aromatic hydrocarbons by means of single-electron-transfer steps depend on alkali metals, ammonia, and cryogenic reaction conditions. In contrast, 2-naphthoyl-coenzyme A (2-NCoA) and 5,6-dihydro-2-NCoA (5,6-DHNCoA) reductases catalyze two two-electron reductions of the naphthoyl-ring system to tetrahydronaphthoyl-CoA at ambient temperature. Using a number of substrate analogues, we provide evidence for a Meisenheimer complex-analogous intermediate during 2-NCoA reduction, whereas the subseq… Show more
“…Only little space is left at the cavity bottom of NCR beyond the distal phenyl ring of the substrate. This observation is in agreement with the ability of NCR to convert 6-F-NCoA but not the bulkier 2-phenanthroyl-CoA 14,16 .Fig. 5Binding site of NCoA.…”
Section: Resultssupporting
confidence: 84%
“…The observed defluorination of 6-F-2-NCoA to 2-NCoA by NCR is in agreement with a hydride transfer to C6 followed by protonation of the thioester-stabilized intermediate at C5 (Fig. 1) 16 . However, the redox potential of the NCoA/5,6-DHNCoA couple is with E °’ = −493 mV 13 outside the range of known biological hydride carriers such as NAD(P)H, flavins or deazaflavins (F420) with E ’° values ranging between ≈0 and −340 mV 17–22 .…”
Section: Introductionsupporting
confidence: 81%
“…It belongs to a distinct subclass of the old yellow enzyme (OYE) family of flavoproteins that are composed of three domains binding FMN (flavin mononucleotide), a [4Fe–4S] cluster and either ADP or flavin adenine dinucleotide (FAD) 13 . Recent studies showed that NCoA reduction in D 2 O enantioselectively yielded the product with the (5 S , 6 S )-configuration 16 . The observed defluorination of 6-F-2-NCoA to 2-NCoA by NCR is in agreement with a hydride transfer to C6 followed by protonation of the thioester-stabilized intermediate at C5 (Fig.…”
Hydride transfers play a crucial role in a multitude of biological redox reactions and are mediated by flavin, deazaflavin or nicotinamide adenine dinucleotide cofactors at standard redox potentials ranging from 0 to –340 mV. 2-Naphthoyl-CoA reductase, a key enzyme of oxygen-independent bacterial naphthalene degradation, uses a low-potential one-electron donor for the two-electron dearomatization of its substrate below the redox limit of known biological hydride transfer processes at
E
°’ = −493 mV. Here we demonstrate by X-ray structural analyses, QM/MM computational studies, and multiple spectroscopy/activity based titrations that highly cooperative electron transfer (
n
= 3) from a low-potential one-electron (FAD) to a two-electron (FMN) transferring flavin cofactor is the key to overcome the resonance stabilized aromatic system by hydride transfer in a highly hydrophobic pocket. The results evidence how the protein environment inversely functionalizes two flavins to switch from low-potential one-electron to hydride transfer at the thermodynamic limit of flavin redox chemistry.
“…Only little space is left at the cavity bottom of NCR beyond the distal phenyl ring of the substrate. This observation is in agreement with the ability of NCR to convert 6-F-NCoA but not the bulkier 2-phenanthroyl-CoA 14,16 .Fig. 5Binding site of NCoA.…”
Section: Resultssupporting
confidence: 84%
“…The observed defluorination of 6-F-2-NCoA to 2-NCoA by NCR is in agreement with a hydride transfer to C6 followed by protonation of the thioester-stabilized intermediate at C5 (Fig. 1) 16 . However, the redox potential of the NCoA/5,6-DHNCoA couple is with E °’ = −493 mV 13 outside the range of known biological hydride carriers such as NAD(P)H, flavins or deazaflavins (F420) with E ’° values ranging between ≈0 and −340 mV 17–22 .…”
Section: Introductionsupporting
confidence: 81%
“…It belongs to a distinct subclass of the old yellow enzyme (OYE) family of flavoproteins that are composed of three domains binding FMN (flavin mononucleotide), a [4Fe–4S] cluster and either ADP or flavin adenine dinucleotide (FAD) 13 . Recent studies showed that NCoA reduction in D 2 O enantioselectively yielded the product with the (5 S , 6 S )-configuration 16 . The observed defluorination of 6-F-2-NCoA to 2-NCoA by NCR is in agreement with a hydride transfer to C6 followed by protonation of the thioester-stabilized intermediate at C5 (Fig.…”
Hydride transfers play a crucial role in a multitude of biological redox reactions and are mediated by flavin, deazaflavin or nicotinamide adenine dinucleotide cofactors at standard redox potentials ranging from 0 to –340 mV. 2-Naphthoyl-CoA reductase, a key enzyme of oxygen-independent bacterial naphthalene degradation, uses a low-potential one-electron donor for the two-electron dearomatization of its substrate below the redox limit of known biological hydride transfer processes at
E
°’ = −493 mV. Here we demonstrate by X-ray structural analyses, QM/MM computational studies, and multiple spectroscopy/activity based titrations that highly cooperative electron transfer (
n
= 3) from a low-potential one-electron (FAD) to a two-electron (FMN) transferring flavin cofactor is the key to overcome the resonance stabilized aromatic system by hydride transfer in a highly hydrophobic pocket. The results evidence how the protein environment inversely functionalizes two flavins to switch from low-potential one-electron to hydride transfer at the thermodynamic limit of flavin redox chemistry.
“…Both enzymatic reactions have demonstrated high stereoselectivity (30-fold improvement) in aqueous solution at ambient temperature. Moreover, these bio-catalysts provide an enantioselective pathway to products that are not readily accessible via Birch reductions [28]. The biosynthesis of polyunsaturated fatty acids (PUFAs) requires ∆12 and ω3 fatty acid desaturases to form the second and third double bonds in the molecule, respectively, as PUFAs are crucial building blocks of membrane glycerolipids and predecessors of signaling molecules in cells.…”
Nowadays, biocatalysts have received much more attention in chemistry regarding their potential to enable high efficiency, high yield, and eco-friendly processes for a myriad of applications. Nature’s vast repository of catalysts has inspired synthetic chemists. Furthermore, the revolutionary technologies in bioengineering have provided the fast discovery and evolution of enzymes that empower chemical synthesis. This article attempts to deliver a comprehensive overview of the last two decades of investigation into enzymatic reactions and highlights the effective performance progress of bio-enzymes exploited in organic synthesis. Based on the types of enzymatic reactions and enzyme commission (E.C.) numbers, the enzymes discussed in the article are classified into oxidoreductases, transferases, hydrolases, and lyases. These applications should provide us with some insight into enzyme design strategies and molecular mechanisms.
“…In contrast, the bicyclic naphthalene is not converted via BzCoA but via 2‐naphthoyl‐CoA (Estelmann et al ., ). Here, reduction to the 5,6‐dihydro‐2‐naphthoyl‐CoA is accomplished by unusual low‐potential hydride transfer at an active site flavin mononucleotide (FMN) (Willistein et al ., , ). However, the reduction of the down‐stream intermediate 5,6,7,8‐tetrahydro‐2‐naphthoyl‐CoA requires again a BCR‐type enzyme to accomplish reduction of the remaining aromatic ring (Eberlein et al ., ).…”
Summary
Benzoyl‐CoA reductases (BCRs) catalyse a key reaction in the anaerobic degradation pathways of monocyclic aromatic substrates, the dearomatization of benzoyl‐CoA (BzCoA) to cyclohexa‐1,5‐diene‐1‐carboxyl‐CoA (1,5‐dienoyl‐CoA) at the negative redox potential limit of diffusible enzymatic substrate/product couples (E°′ = −622 mV). A 1‐MDa class II BCR complex composed of the BamBCDEGHI subunits has so far only been isolated from the Fe(III)‐respiring Geobacter metallireducens. It is supposed to drive endergonic benzene ring reduction at an active site W‐pterin cofactor by flavin‐based electron bifurcation. Here, we identified multiple copies of putative genes encoding the structural components of a class II BCR in sulfate reducing, Fe(III)‐respiring and syntrophic bacteria. A soluble 950 kDa Bam[(BC)2DEFGHI]2 complex was isolated from extracts of Desulfosarcina cetonica cells grown with benzoate/sulfate. Metal and cofactor analyses together with the identification of conserved binding motifs gave rise to 4 W‐pterins, two selenocysteines, six flavin adenine dinucleotides, four Zn, and 48 FeS clusters. The complex exhibited 1,5‐dienoyl‐CoA‐, NADPH‐ and ferredoxin‐dependent oxidoreductase activities. Our results indicate that high‐molecular class II BCR metalloenzyme machineries are remarkably conserved in strictly anaerobic bacteria with regard to subunit architecture and cofactor content, but their subcellular localization and electron acceptor preference may differ as a result of adaptations to variable energy metabolisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
