Novel Biocatalysts from Specialized Metabolism

Kries, Hajo; Trottmann, Felix; Hertweck, Christian

doi:10.1002/anie.202309284

Cited by 4 publications

(1 citation statement)

References 106 publications

(183 reference statements)

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“…The immobilization of enzymes facilitates the use of enzymatic catalysis with non-polar substrates and additionally suppresses water-driven side reactions, dramatically increasing their versatility in synthetic chemistry. Among many others, enzymes have found uses in synthetic chemistry as biocatalytic alternatives of existing synthetic procedures [ 15 ], chiral resolution of racemic substrates [ 16 ], oxidation catalysts [ 17 ], and as catalysts for carbon–carbon bond formation reactions [ 18 ]. Due to society’s extensive use of polymer materials, specific emphasis has been placed on the development of enzymes as environmentally friendly polymerization catalysts.…”

Section: Introductionmentioning

confidence: 99%

Enzymes in “Green” Synthetic Chemistry: Laccase and Lipase

Scheibel,

Gitsov,

Gitsov

2024

Molecules

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Enzymes play an important role in numerous natural processes and are increasingly being utilized as environmentally friendly substitutes and alternatives to many common catalysts. Their essential advantages are high catalytic efficiency, substrate specificity, minimal formation of byproducts, and low energy demand. All of these benefits make enzymes highly desirable targets of academic research and industrial development. This review has the modest aim of briefly overviewing the classification, mechanism of action, basic kinetics and reaction condition effects that are common across all six enzyme classes. Special attention is devoted to immobilization strategies as the main tools to improve the resistance to environmental stress factors (temperature, pH and solvents) and prolong the catalytic lifecycle of these biocatalysts. The advantages and drawbacks of methods such as macromolecular crosslinking, solid scaffold carriers, entrapment, and surface modification (covalent and physical) are discussed and illustrated using numerous examples. Among the hundreds and possibly thousands of known and recently discovered enzymes, hydrolases and oxidoreductases are distinguished by their relative availability, stability, and wide use in synthetic applications, which include pharmaceutics, food and beverage treatments, environmental clean-up, and polymerizations. Two representatives of those groups—laccase (an oxidoreductase) and lipase (a hydrolase)—are discussed at length, including their structure, catalytic mechanism, and diverse usage. Objective representation of the current status and emerging trends are provided in the main conclusions.

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Section: Introductionmentioning

confidence: 99%

Enzymes in “Green” Synthetic Chemistry: Laccase and Lipase

Scheibel,

Gitsov,

Gitsov

2024

Molecules

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Discovery and Engineering of a Bacterial (+)‐Pulegone Reductase for Efficient (−)‐Menthol Biosynthesis

Wu,

Li,

Liu

et al. 2024

ChemSusChem

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The biosynthesis of valuable plant‐derived monoterpene (–)‐menthol from readily available feedstocks (e.g., (–)‐limonene) is of great significance because of the high market demand for this product. However, biotransforming (+)‐pulegone into (–)‐menthone, the (–)‐menthol precursor, through (+)‐pulegone reductase (PGR) catalysis is inefficient because of the poor protein expression or catalytic efficiency (kcat/Km) of plant origin PGRs. In this study, a novel bacterial PGR from Pseudomonas resinovorans (PrPGR) was identified, and the most successful variant, PrPGRM2‐1 (A50V/G53W), was obtained, showing respective 20‐fold and 204‐fold improvements in specific activity and catalytic efficiency. PrPGRM2‐1 was employed to bioreduce (+)‐pulegone, resulting in 4.4‐fold and 35‐fold enhancements in (–)‐menthone titers compared with the bioreductions catalyzed by wild‐type (WT) PrPGR and MpPGR, respectively. Furthermore, a whole‐cell biocatalyst containing PrPGRM2‐1, MpMMR, and BstFDH was constructed and achieved the highest (–)‐menthol titer reported to date without externally supplemented NADPH/NADP+. Overall, this study details an efficient PGR with high catalytic efficiency that possesses great potential for (–)‐menthol biosynthesis.

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Highly Stereoselective Biocatalytic One-Pot Synthesis of Chiral Saturated Oxygen Heterocycles by Integration of a Biosynthetic Heterocyclase into Multiple-Enzyme Cascades

Roß-Taschner,

Derra,

Stang

et al. 2024

ACS Catal.

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The secondary metabolism is a rich source of enzymes with new synthetically attractive activities that have not yet been integrated into the toolbox of biocatalysis. Chiral saturated oxygen heterocycles (CSOHs) are abundant structural elements of natural products and other value-added compounds. We present a biocatalytic method for the synthesis of CSOHs from readily accessible precursors that combines an intramolecular oxa-Michael addition (IMOMA)-catalyzing cyclase (CYC) from a biosynthetic pathway with alcohol dehydrogenases (ADHs) and thioester-derivatizing enzymes. The one-pot ADH–CYC reaction enables access to various tetrahydropyran (THP) and tetrahydrofuran thioesters under control of up to four stereocenters. These products are readily convertible into useful CSOH ketone, amide, aldehyde/alcohol, ester, and carboxylic acid building blocks by chemical and enzymatic means. The extendibility to more complex multienzyme cascades was demonstrated by the addition of a thioesterase and a carboxylic acid reductase, allowing the straightforward chemoenzymatic synthesis of the natural product (−)-civet, a new derivative, and a THP alcohol. The integration of IMOMA cyclases into enzymatic cascades allows better exploitation of the high synthetic potential of this new group of ring-forming enzymes and expands the repertoire for the synthesis of pharmacologically relevant CSOHs as a highly selective and versatile alternative. This approach will be adaptable for the synthesis of a wide range of CSOHs by varying ADHs, IMOMA cyclases, and modifying enzymes.

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Novel Biocatalysts from Specialized Metabolism

Cited by 4 publications

References 106 publications

Enzymes in “Green” Synthetic Chemistry: Laccase and Lipase

Enzymes in “Green” Synthetic Chemistry: Laccase and Lipase

Discovery and Engineering of a Bacterial (+)‐Pulegone Reductase for Efficient (−)‐Menthol Biosynthesis

Highly Stereoselective Biocatalytic One-Pot Synthesis of Chiral Saturated Oxygen Heterocycles by Integration of a Biosynthetic Heterocyclase into Multiple-Enzyme Cascades

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