One‐Pot Biocatalytic Double Oxidation of α‐Isophorone for the Synthesis of Ketoisophorone

Tavanti, Michele; Parmeggiani, Fabio; Castellanos, J. Rubén Gómez; Mattevi, Andrea; Turner, Nicholas J.

doi:10.1002/cctc.201700620

Cited by 35 publications

(33 citation statements)

References 93 publications

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“…The chemical route towards some of these compounds comprises the isomer-ization of α-isophorone to β-isophorone and the further oxidation of this, to ketoisophorone (KET). [16] In this same line, Shaghayegh et al compared the performance of two P450 (CYP102 A1 and CYP101 A1) for the hydroxylation of ISO, however, background activity from the E. coli host cells converted the recently formed KET to levodione. [9] The direct selective allylic oxidation of ISO to KET has also been demonstrated, nevertheless, it makes use of toxic heavy metals, yields undesired by-products and/or requires harsh conditions.…”

Section: Introductionmentioning

confidence: 99%

Ketoisophorone Synthesis with an Immobilized Alcohol Dehydrogenase

Solé

Brummund²,

Caminal

et al. 2019

ChemCatChem

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The monoterpenoid α-isophorone is sourced from the available and renewable plant dry matter, as well as a waste recovery operation from acetone. This compound, can be hydroxylated to 4-hydroxy-isophorone which is the main precursor for the synthesis of ketoisophorone. On its turn, ketoisophorone is a key intermediate for the production of carotenoids and Vitamin E. Here, the enzymatic oxidation of 4-hydroxy-isophorone to ketoisophorone is demonstrated employing an alcohol dehydrogenase (ADHaa) from Artemisia annua and a NADPH oxidase (NOX), as a cofactor regeneration enzyme. After 24 h of reaction and an initial substrate concentration of 50 mM, 95.7 % yield and a space time yield of 6.52 g L À 1 day À 1 could be obtained. Furthermore, the immobilization of the alcohol dehydrogenase was studied on 17 different supports. An epoxy-functionalized agarose resulted in the highest metrics, 100 � 0% immobilization yield and 58.2 � 3.5 % retained activity. Finally, the immobilized ADHaa was successfully implemented in 4 reaction cycles (96 h operation) presenting a biocatalyst yield of 23.4 g product g À 1 of enzyme. It represents a 2.5-fold increase compared with the reaction with soluble enzymes.

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Section: Introductionmentioning

confidence: 99%

Ketoisophorone Synthesis with an Immobilized Alcohol Dehydrogenase

Solé

Brummund²,

Caminal

et al. 2019

ChemCatChem

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“…Very recently, Turner et al. developed double allylic oxidation of α‐isophorone to ketoisophorone, a useful synthon for bioactive compound (Scheme a) . By evolving a self‐sufficient P450cam‐RhFRed, a P450‐WAL was obtained with much better activity and regioselectivity for hydroxylation of α‐isophorone to ( R )‐4‐hydroxy‐α‐isophorone.…”

Section: Recent Development Of Whole‐cell Cascade Biotransformationsmentioning

confidence: 99%

“… Cascade biotransformations of terpene derivatives. a) Double oxidation of α‐isophorone to ketoisophorone with E. coli cells; b) conversion of limonene to a chiral carvolactone with P. pudita and E. coli cells …”

Section: Recent Development Of Whole‐cell Cascade Biotransformationsmentioning

confidence: 99%

Whole‐Cell Cascade Biotransformations for One‐Pot Multistep Organic Synthesis

2018

ChemCatChem

104

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Performing one‐pot multi‐catalysis reactions is a revolutionary tool for multistep synthesis, representing a fast‐developing theme in catalysis field. To develop cascade reactions, enzymes are ideal catalysts due to their compatible reaction conditions. The implementation of enzyme cascades in recombinant microbial cells provides easily available self‐replicating catalysts for facile one‐pot biotransformations to produce a wide range of high‐value (chiral) chemicals. In this minireview, we summarize the recent development of whole‐cell cascade biotransformations according to the types of substrates, ranging from petrochemicals to biochemicals. Furthermore, we provide general instructions for the establishment of in vivo enzyme cascades, discuss the encountered problems and the corresponding solutions, and highlight the promising directions for future advance.

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“…An example for a cascade with interconnected two oxidation steps is provided below. The double oxidation of α ‐isophorone ( α ‐IP) to ketoisophorone was enabled by combining a P450 monooxygenase and an ADH (Scheme ) . Variants of the self‐sufficient P450cam‐RhFRed with improved activity have been identified to perform the regio‐ and enantioselective allylic oxidation of α ‐IP to 4‐hydroxy‐ α ‐isophorone as the first step.…”

Section: In Vitro Cascades Requiring For Each Step a Biocatalystmentioning

confidence: 99%

Extending Designed Linear Biocatalytic Cascades for Organic Synthesis

2018

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Artificial cascade reactions involving biocatalysts have demonstrated a tremendous potential during the recent years. This review just focuses on selected examples of the last year and putting them into context to a previously published suggestion for classification. Subdividing the cascades according to the number of catalysts in the linear sequence, and classifying whether the steps are performed simultaneous or in a sequential fashion as well as whether the reaction sequence is performed in vitro or in vivo allows to organise the concepts. The last year showed, that combinations of in vivo as well as in vitro are possible. Incompatible reaction steps may be run in a sequential fashion or by compartmentalisation of the incompatible steps either by using special reactors (membrane), polymersomes or flow techniques.

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One‐Pot Biocatalytic Double Oxidation of α‐Isophorone for the Synthesis of Ketoisophorone

Cited by 35 publications

References 93 publications

Ketoisophorone Synthesis with an Immobilized Alcohol Dehydrogenase

Ketoisophorone Synthesis with an Immobilized Alcohol Dehydrogenase

Whole‐Cell Cascade Biotransformations for One‐Pot Multistep Organic Synthesis

Extending Designed Linear Biocatalytic Cascades for Organic Synthesis

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