Recent Developments in Flavin‐Based Catalysis

Brondani, Patrícia Bulegon; Fraaije, Marco W.; Gonzalo, Gonzalo de

doi:10.1002/9781118828083.ch6

Cited by 9 publications

(12 citation statements)

References 68 publications

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“…Accessing optically pure epoxides and sulfoxides via biocatalytic approaches is a current issue [73] and several mono-and dioxygenases, as well as peroxygenases and epoxide hydrolases, have been employed to reach this goal. [45,66,74,75] However, there are still hindrances concerning process stability, due to inactivation or degradation of the enzyme, limited substrate scope and/or insufficient product purity and quality. While biocatalysts are yet attractive for the generation of green processes, it is, therefore, necessary to look for alternative enzymes that can meet the requirements mentioned above.…”

Section: Discussionmentioning

confidence: 99%

“…As a consequence, they are currently considered as candidates for biotechnological processes. [1,3,9,44,45] However, limited activity, stability and conversion of bulky substrates have been issues within this group of flavoproteins. Furthermore, changing or even optimizing the enantioselectivity of these biocatalysts is of high interest.…”

Section: Introductionmentioning

confidence: 99%

“…As this indicates, that a high biotechnological potential might be yet unexplored, we cloned and expressed 31 putative SMOs and IMOs to span the whole range of GEMs. Selected candidates were characterized in detail and besides styrene, we applied 11 sulfides as model substrates for the biosynthesis of chiral sulfoxides (Scheme 2), which are of great value for industrial, pharmaceutical and agrochemical applications (reviewed in Ref [45,48]). Sulfide biotransformations were scaled up using the most promising SMOs together with the nicotinamide cofactor mimic 1-benzyl-1,4-dihydronicotinamide (BNAH) for regeneration of reduced FAD.…”

Section: Introductionmentioning

confidence: 99%

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Accessing Enantiopure Epoxides and Sulfoxides: Related Flavin‐Dependent Monooxygenases Provide Reversed Enantioselectivity

et al. 2019

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Enantiopure organic compounds are of major importance for the chemical and pharmaceutical industry. Flavin‐dependent group E monooxygenases, composed of monooxygenase and reductase, are known to perform epoxidation of substituted alkenes as well as sulfoxidation in a regio‐ and enantioselective fashion. Group E is divided into styrene monooxygenases (SMO) and indole monooxygenases (IMO). Hitherto mainly SMOs have been characterized. In this study, we assayed 31 monooxygenases from both types, while 23 of which showed activity. They almost exclusively produced (S)‐styrene oxide at high enantiomeric excess with maximum activities of 0.73 μmol min−1 mg−1 (kcat=0.54 s−1). In case of sulfoxidation, we found that the enantioselectivity is contrary between both types. IMOs preferably produce the (S)‐enantiomer while SMOs have a tendency to produce the (R)‐enantiomer. Sequence analysis and molecular docking of substrates allowed identifying fingerprint motives: SMO N46‐V48‐H50‐Y73‐H76‐S96 and IMO S46‐Q48‐M50‐V/I73‐I76‐A96. These form an essential part of the active site while the loop (AS44‐51) interacts with the co‐substrate and other amino acids direct the substrate. The motives clearly distinguish group E monooxygenases and define the enantioselectivity and thus direct biotechnological applications. Two‐hour biotransformations with several sulfides in conjunction with upscale experiments (10 and 100 mg scale) resulted in the identification of promising candidates for the realization of biocatalytic processes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Accessing Enantiopure Epoxides and Sulfoxides: Related Flavin‐Dependent Monooxygenases Provide Reversed Enantioselectivity

et al. 2019

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“…They are mainly known to catalyse Baeyer-Villiger oxidations by incorporating a single oxygen atom adjacent to the carbonyl carbon to form an ester or lactone. Yet, BVMOs are also capable of carrying out other oxygenation reactions such as epoxidations [15] and sulfoxidations [16]. The oxygen atom inserted in the substrate comes from molecular oxygen while an external reductant such as NAD(P)H is required.…”

Section: Introductionmentioning

confidence: 99%

Conversion of Furans by Baeyer-Villiger Monooxygenases

Kumar

Fraaije

2017

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Various furans are considered as valuable platform chemicals as they can be derived from plant biomass. Yet, for their exploitation, follow-up chemistry is required. Here we demonstrate that Baeyer-Villiger monooxygenases (BVMOs) can be used as biocatalysts for the selective oxidation of several furans, including 5-(hydroxymethyl) furfural (HMF) and furfural. A total of 15 different BVMOs were tested for their activity on furfural, which revealed that most of the biocatalysts were active on this aromatic aldehyde. Phenylacetone monooxygenase (PAMO) and a mutant thereof (PAMO M446G ) were selected for studying their biocatalytic potential in converting furfural and some other furans. While BVMOs are usually known to form an ester or lactone as a 'normal' product by inserting an oxygen atom adjacent to the carbonyl carbon of the substrate, our results reveal that both biocatalysts produce furanoid acids as the main product from the corresponding aldehydes. Altogether, our study shows that BVMOs can be employed for the selective oxidation of furans.

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“…Several methodologies, employing different catalysts, have been described for their preparation [5,6]. Biocatalytic procedures present some advantages, such as the use of mild and environmentally friendly reaction conditions and oxidants [7,8]. Several types of oxidative enzymes can be used for the synthesis of chiral sulfoxides, which include peroxidases [9][10][11], dioxygenases [12,13] and different types of monooxygenases [14,15].…”

Section: Introductionmentioning

confidence: 99%

Polycyclic Ketone Monooxygenase (PockeMO): A Robust Biocatalyst for the Synthesis of Optically Active Sulfoxides

2017

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Abstract:A recently discovered, moderately thermostable Baeyer-Villiger monooxygenase, polycyclic ketone monooxygenase (PockeMO), from Thermothelomyces thermophila has been employed as a biocatalyst in a set of asymmetric sulfoxidations. The enzyme was able to catalyze the oxidation of various alkyl aryl sulfides with good selectivities and moderate to high activities. The biocatalytic performance was able to be further increased by optimizing some reaction parameters, such as the addition of 10% v v −1 of water miscible solvents or toluene, or by performing the conversion at a relatively high temperature (45 • C). PockeMO was found to display an optimum activity at sulfide concentrations of 50 mM, while it can also function at 200 mM. Taken together, the data show that PockeMO can be used as robust biocatalyst for the synthesis of optically active sulfoxides.

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Recent Developments in Flavin‐Based Catalysis

Cited by 9 publications

References 68 publications

Accessing Enantiopure Epoxides and Sulfoxides: Related Flavin‐Dependent Monooxygenases Provide Reversed Enantioselectivity

Accessing Enantiopure Epoxides and Sulfoxides: Related Flavin‐Dependent Monooxygenases Provide Reversed Enantioselectivity

Conversion of Furans by Baeyer-Villiger Monooxygenases

Polycyclic Ketone Monooxygenase (PockeMO): A Robust Biocatalyst for the Synthesis of Optically Active Sulfoxides

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