Regio- and stereoselective synthesis of chiral nitrilolactones using Baeyer–Villiger monooxygenases

Fink, Michael; Šnajdrová, Radka; Winninger, Alexander; Mihovilovic, Marko D.

doi:10.1016/j.tet.2015.12.047

Cited by 8 publications

(10 citation statements)

References 32 publications

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“…Owing to electronic, steric, and conformational effects, the abnormal product is not accessible through chemical Baeyer–Villiger oxidation. However, the formation of the abnormal product by BVMOs was reported for a number of reactions, such as the conversions of chiral nitrilolactones, terpenones, β‐amino ketones, β‐hydroxy ketones, and bicyclic ketones . Divergent regioselectivities for different BVMOs have also been observed for the conversion of aldehydes into formates or carboxylic acids and long‐chain ketocarboxylic acids .…”

Section: Introductionmentioning

confidence: 99%

“…CHMO Arthro was characterized and recombinantly expressed in 2003 . This enzyme was used to study the conversion of terpenones, β‐amino ketones, and nitrilolactones . OTEMO is involved in the camphor degradation pathway of Pseudomonas putida ATCC17453, in which it converts 2‐oxo‐Δ 3 ‐4,5,5‐trimethylcyclopentenylacetyl‐CoA into the corresponding lactone.…”

Section: Introductionmentioning

confidence: 99%

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Controlling the Regioselectivity of Baeyer–Villiger Monooxygenases by Mutation of Active‐Site Residues

2017

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Baeyer-Villiger monooxygenase (BVMO)-mediated regiodivergent conversions of asymmetric ketones can lead to the formation of "normal" or "abnormal" lactones. In a previous study, we were able to change the regioselectivity of a BVMO by mutation of the active-site residues to smaller amino acids, which thus created more space. In this study, we demonstrate that this method can also be used for other BVMO/substrate combinations. We investigated the regioselectivity of 2-oxo-Δ -4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase from Pseudomonas putida (OTEMO) for cis-bicyclo[3.2.0]hept-2-en-6-one (1) and trans-dihydrocarvone (2), and we were able to switch the regioselectivity of this enzyme for one of the substrate enantiomers. The OTEMO wild-type enzyme converted (-)-1 into an equal (50:50) mixture of the normal and abnormal products. The F255A/F443V variant produced 90 % of the normal product, whereas the W501V variant formed up to 98 % of the abnormal product. OTEMO F255A exclusively produced the normal lactone from (+)-2, whereas the wild-type enzyme was selective for the production of the abnormal product. The positions of these amino acids were equivalent to those mutated in the cyclohexanone monooxygenases from Arthrobacter sp. and Acinetobacter sp. (CHMO and CHMO ) to switch their regioselectivity towards (+)-2, which suggests that there are hot spots in the active site of BVMOs that can be targeted with the aim to change the regioselectivity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Controlling the Regioselectivity of Baeyer–Villiger Monooxygenases by Mutation of Active‐Site Residues

2017

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“…Two BVMOs were already known to accept the OCHPN ketone, but the described catalysts preferentially converted the (R)-enantiomer, leaving the (S)-ketone untouched, or oxidizing it at a very low rate (Berezina et al, 2007). We found this trend to hold true for many other BVMOs (Fink et al, 2015).…”

Section: Resultsmentioning

confidence: 54%

“…Therefore, it was important to find a non-selective enzyme. In the course of a systematic study on BVMO-catalyzed oxidations of nitriloketones (Fink et al, 2015), experiments on an analytical scale showed that a cyclopentadecanone monooxygenase (CPDMO) from Pseudomonas sp. NCIMB 9872 (Clouthier et al, 2006;Reetz et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…S1). In the course of a systematic study on BVMO-catalyzed oxidations of nitriloketones (Fink et al, 2015), experiments on an analytical scale showed that a cyclopentadecanone monooxygenase (CPDMO) from Pseudomonas sp. HI-70 (Iwaki et al, 2006) catalyzed the transformation of both starting material enantiomers with low selectivity (E ¼ 5-16) and at a high rate.…”

Section: Resultsmentioning

confidence: 99%

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Non‐hazardous biocatalytic oxidation in Nylon‐9 monomer synthesis on a 40 g scale with efficient downstream processing

Milker

Fink

Rudroff

et al. 2017

Biotech & Bioengineering

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This paper describes the development of a biocatalytic process on the multi-dozen gram scale for the synthesis of a precursor to Nylon-9, a specialty polyamide. Such materials are growing in demand, but their corresponding monomers are often difficult to synthesize, giving rise to biocatalytic approaches. Here, we implemented cyclopentadecanone monooxygenase as an Escherichia coli whole-cell biocatalyst in a defined medium, together with a substrate feeding-product removal concept, and an optimized downstream processing (DSP). A previously described hazardous peracid-mediated oxidation was thus replaced with a safe and scalable protocol, using aerial oxygen as oxidant, and water as reaction solvent. The engineered process converted 42 g (0.28 mol) starting material ketone to the corresponding lactone with an isolated yield of 70% (33 g), after highly efficient DSP with 95% recovery of the converted material, translating to a volumetric yield of 8 g pure product per liter. Biotechnol. Bioeng. 2017;114: 1670-1678. © 2017 Wiley Periodicals, Inc.

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Hot spots for the protein engineering of Baeyer-Villiger monooxygenases

Balke

Beier

Bornscheuer

2018

Biotechnology Advances

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Regio- and stereoselective synthesis of chiral nitrilolactones using Baeyer–Villiger monooxygenases

Cited by 8 publications

References 32 publications

Controlling the Regioselectivity of Baeyer–Villiger Monooxygenases by Mutation of Active‐Site Residues

Controlling the Regioselectivity of Baeyer–Villiger Monooxygenases by Mutation of Active‐Site Residues

Non‐hazardous biocatalytic oxidation in Nylon‐9 monomer synthesis on a 40 g scale with efficient downstream processing

Hot spots for the protein engineering of Baeyer-Villiger monooxygenases

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