Biocatalytic Synthesis of Natural Products by<scp><i>O</i></scp>‐Methyltransferases

Wessjohann, Ludger A.; Bauer, Anne‐Katrin; Dippe, Martin; Ley, Jakob P.; Geißler, Torsten

doi:10.1002/9783527677122.ch7

Cited by 3 publications

(5 citation statements)

References 81 publications

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“…They are abundant in the biosynthetic pathways of a diverse range of natural products [ 2 ]. In plants, OMTs often contributes to the biosynthesis of compounds related to flower scents, pigments, or phytoalexins that play important roles in biological interaction [ 3 ]. OMTs also function in methylation of plant secondary metabolites including alkaloids, isoprenoids and phenolic compounds [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Cloning and Characterization of a meta/para-O-Methyltransferase from Lycoris aurea

Sun

Wang

Ren

et al. 2018

IJMS

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O-methyltransferases (OMTs) have been demonstrated to play key roles in the biosynthesis of plant secondary metabolites, such as alkaloids, isoprenoids, and phenolic compounds. Here, we isolated and characterized an OMT gene from Lycoris aurea (namely LaOMT1), based on our previous transcriptome sequencing data. Sequence alignment and phylogenetic analysis showed that LaOMT1 belongs to the class I OMT, and shares high identity to other known plant OMTs. Also, LaOMT1 is highly identical in its amino acid sequence to NpN4OMT, a norbelladine 4′-OMT from Narcissus sp. aff. pseudonarcissus involved in the biosynthesis of Amaryllidaceae alkaloids. Biochemical analysis indicated that the recombinant LaOMT1 displayed both para and meta O-methylation activities with caffeic acid and 3,4-dihydroxybenzaldehyde, and showed a strong preference for the meta position. Besides, LaOMT1 also catalyzes the O-methylation of norbelladine to form 4′-O-methylnorbelladine, which has been demonstrated to be a universal precursor of all the primary Amaryllidaceae alkaloid skeletons. The results from quantitative real-time PCR assay indicated that LaOMT1 was ubiquitously expressed in different tissues of L. aurea, and its highest expression level was observed in the ovary. Meanwhile, the largest concentration of lycorine and galanthamine were found in the ovary, whereas the highest level of narciclasine was observed in the bulb. In addition, sodium chloride (NaCl), cold, polyethylene glycol (PEG), sodium nitroprusside (SNP), and methyl jasmonate (MeJA) treatments could significantly increase LaOMT1 transcripts, while abscisic acid (ABA) treatment dramatically decreased the expression level of LaOMT1. Subcellular localization showed that LaOMT1 is mainly localized in cytoplasm and endosome. Our results in this study indicate that LaOMT1 may play a multifunctional role, and lay the foundation for Amaryllidaceae alkaloid biosynthesis in L. aurea.

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Section: Introductionmentioning

confidence: 99%

Molecular Cloning and Characterization of a meta/para-O-Methyltransferase from Lycoris aurea

Sun

Wang

Ren

et al. 2018

IJMS

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“…Biocatalytic modifications of natural products (NPs) take place in all living organisms and cause changes in the molecules' physicochemical properties such as their solubility, lipophilicity, and pKs. [57] Such modifications can be used for the improvement of, for example, the stability or bioavailability of drugs. In this section, four types of biocatalytic modifications will be discussed: oxidations, O-methylations, phosphorylations, and halogenations.…”

Section: Late-stage Functionalizationmentioning

confidence: 99%

“…It leads to the rare phytochemical ponciretin, which is known for its anti-inflammatory properties (Scheme 19). [57,64]…”

Section: Biocatalytic Modification Of Nps By Oxidation Reactionsmentioning

confidence: 99%

“…The natural molecule is not biologically active but exhibits anticancer properties when methylated through an O-methyltransferase (OMT). [57] OMTs accept many different possess high specificity and regioselectivity and form products in high example of their successful application is the biotransformation of Scheme 20. Three-enzyme, one-pot in vitro reaction for the activation of sugars with GDP.…”

Section: Biocatalytic Modification Of Nps By O-methylation Reactionsmentioning

confidence: 99%

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The Development of Biocatalysis as a Tool for Drug Discovery

Schwarz

Rosenthal

Šnajdrová

et al. 2020

Chimia

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Enzymes are versatile biocatalysts capable of performing selective reactions. The advantages of enzymes in comparison to classical chemistry including chemical catalysts are the generally milder process conditions and avoidance of harmful reactants. Their high selectivity and specificity are especially beneficial for the enzymatic synthesis of new products with potential applications in drug research. Therefore, in the past decades, the utilization of isolated enzymes or whole-cell biocatalysts has spread through a growing number of biotechnological industries. The applications comprise the production of chiral building blocks for the pharmaceutical and fine chemical industry, the enzymatic synthesis of drug metabolites for testing of toxicity, function, biological activity, degradation and the production of biocatalytically modified natural products, which all play a role in drug discovery. Especially Oreste Ghisalba's contributions, which paved the way for the industrial use of enzymes, will be considered in this review.

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“…Compared to most other OMTs tested in our group, it turned out to be very well-behaved, stable, easily expressible, and suitable for upscaling to the preparative scale. [19] However, the enzyme is strictly 3'-selective (i. e., vanilloid-motif generating). In this work, rational engineering of PFOMT, using a newly developed, rapid colorimetric assay, yielded variants with improved turnover or inverse specificity, i. e. for para-O-methylation.…”

Section: Introductionmentioning

confidence: 99%

Altering the Regiospecificity of a CatecholO‐methyltransferase through Rational Design: Vanilloid vs. Isovanilloid Motifs in the B‐ring of Flavonoids

et al. 2022

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Rational re-design of the substrate pocket of phenylpropanoidflavonoid O-methyltransferase (PFOMT) from Mesembryanthemum crystallinum, an enzyme that selectively methylates the 3'position (= meta-position) in catechol-moieties of flavonoids to guiacol-moieties, provided the basis for the generation of variants with opposite, i. e. 4'-(para-) regioselectivity and enhanced catalytic efficiency. A double variant (Y51R/N202W) identified through a newly developed colorimetric assay efficiently modified the para-position in flavanone and flavanonol substrates, providing access to the sweetener molecule hesperetin and other rare plant flavonoids having an isovanilloid motif.

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Biocatalytic Synthesis of Natural Products byO‐Methyltransferases

Cited by 3 publications

References 81 publications

Molecular Cloning and Characterization of a meta/para-O-Methyltransferase from Lycoris aurea

Molecular Cloning and Characterization of a meta/para-O-Methyltransferase from Lycoris aurea

The Development of Biocatalysis as a Tool for Drug Discovery

Altering the Regiospecificity of a CatecholO‐methyltransferase through Rational Design: Vanilloid vs. Isovanilloid Motifs in the B‐ring of Flavonoids

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