Library of Norcoclaurine Synthases and Their Immobilization for Biocatalytic Transformations

Lechner, Horst; Soriano, Pablo; Poschner, Roman; Hailes, Helen C.; Ward, John M.; Kroutil, Wolfgang

doi:10.1002/biot.201700542

Cited by 19 publications

(21 citation statements)

References 49 publications

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“…Through the Pictet–Spenglerase reaction, dopamine ( 2 ) becomes the origin of the isoquinoline moiety, and 4‐HPAA ( 3 ) is incorporated into the benzyl moiety, thereby resulting in the benzylisoquinoline nucleus of ( S )‐ 1 . Recent reports using recombinant NCSs from Thalictrum flavum ( Tf NCS), Coptis japonica ( Cj NCS), and Papaver bracteatum ( Pb NCS) have highlighted their versatility in BIA and tetrahydroisoquinoline (THIA) synthesis using a range of aldehydes and several ketones . X‐ray crystallographic and modelling studies have also enhanced our mechanistic understanding .…”

Section: Methodsmentioning

confidence: 99%

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

et al. 2019

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The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher‐yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non‐natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non‐natural alkaloids, in cascades from l‐tyrosine and analogues.

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Section: Methodsmentioning

confidence: 99%

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

et al. 2019

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“…Furthermore, various chiral and spiro‐1,1′‐disubstituted THIQs were biocatalytically synthesized using NCS‐ Tf variants (Figure ). The extension of the substrate scope of NCS was followed by the most recent studies by Lechner et al ., who reported the extension of the panel of Pictet‐Spenglerase NCS and their immobilization for the biocatalytic generation of isoquinoline products . The library of nine various NCSs was initially tested for their ability to condense the dopamine and 4‐HPAA substrate using lyophilized whole cells as biocatalysts.…”

Section: Pictet‐spenglerasesmentioning

confidence: 99%

“…Recent advances in the improvement of substrate scope of the Pictet‐Spenglerase enzymes can form the foundation of biosynthetic pathways in the microbial systems for the generation of novel alkaloids with improved and novel pharmaceutical activities. Additionally, a handful of new enzymes carrying the Pictet‐Spengler reaction such as salsolinol synthase, McbB from Marinactinospora thermotolerans , deacetylisoipecoside synthase, and deacetylipecoside synthase, two novel NCSs from Argemone mexicana (AmNCS1, AmNCS2) and one new NCS from Corydalis saxicola have recently been identified. The development in the understanding of these enzymes will further enrich the biocatalytic synthesis of a myriad of alkaloids with diverse pharmaceutical functions ,…”

Section: Pictet‐spenglerasesmentioning

confidence: 99%

Biocatalyzed C−C Bond Formation for the Production of Alkaloids

2018

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Traditional methods of chemical synthesis of alkaloids exhibit various problems such as lack of enantioselectivity, the use of toxic chemical and intermediates, and multiple numbers of synthetic steps. Consequently, various enzymatic methods for the formation of CÀC bonds in the alkaloid skeleton have been developed. Herein, we report advances achieved in the enzymatic or chemo-enzymatic synthesis of pharmaceutically important alkaloids that employ three CÀC bond forming enzymes: two Pictet-Spenglerases and the oxidative CÀC bond forming flavoenzyme Berberine Bridge Enzyme. Protein engi-neering studies, improving the substrate scope of these enzymes, and thereby leading to the synthesis of non-natural alkaloids possessing higher or newer pharmacological activities, are also discussed. Furthermore, the integration of these biocatalysts with other enzymes, in multi-enzymatic cascades for the enantioselective synthesis of alkaloids, is also reviewed. Current results suggest that these enzymes hold great promise for the generation of CÀC bonds in the selective synthesis of alkaloid compounds possessing diverse pharmacological properties.

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“…[5] Dopamine (2) is generated through ortho-hydroxylation and decarboxylation of l-tyrosine (4)b yatyrosine hydroxylase and DOPA decarboxylase (DODC), respectively.I nap arallel pathway, 4-HPAA (3)i sf ormed through the deamination of 4 to 4hydroxyphenylpyruvate by at yrosine aminotransferase,f ollowed by decarboxylation to 3 by a4-hydroxyphenylpyruvate decarboxylase. [7][8][9][10][11] X-ray crystallographic and modelling studies have also enhanced our mechanistic understanding. Recent reports using recombinant NCSs from Thalictrum flavum (TfNCS), Coptis japonica (CjNCS), and Papaver bracteatum (PbNCS) have highlighted their versatility in BIA and tetrahydroisoquinoline (THIA) synthesis using arange of aldehydes and several ketones.…”

mentioning

confidence: 99%

“…Recent reports using recombinant NCSs from Thalictrum flavum (TfNCS), Coptis japonica (CjNCS), and Papaver bracteatum (PbNCS) have highlighted their versatility in BIA and tetrahydroisoquinoline (THIA) synthesis using arange of aldehydes and several ketones. [7][8][9][10][11] X-ray crystallographic and modelling studies have also enhanced our mechanistic understanding. [12][13][14] In addition, their incorporation into enzymatic and chemoenzymatic cascades to give THIAs in high yields and stereoselectivity has demonstrated their potential in sustainable synthesis.…”

mentioning

confidence: 99%

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

et al. 2019

Self Cite

View full text Add to dashboard Cite

The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides ah igher-yielding strategy than traditional synthetic methods or isolation from plant material. However,t he reconstruction of BIA pathwaysi nm icroorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions.M ost importantly,n on-natural BIAs can be generated through such artificial pathways. In the current study,w ed escribe the use of tyrosinases and decarboxylases and combine these with atransaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs,including six non-natural alkaloids,incascades from ltyrosine and analogues.

show abstract

Library of Norcoclaurine Synthases and Their Immobilization for Biocatalytic Transformations

Cited by 19 publications

References 49 publications

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

Biocatalyzed C−C Bond Formation for the Production of Alkaloids

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

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