A roadmap for metagenomic enzyme discovery

Robinson, Serina L.; Piel, Jörn; Sunagawa, Shinichi

doi:10.1039/d1np00006c

Cited by 100 publications

(67 citation statements)

References 303 publications

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“…As a future direction, the substrate scope and activity of MAOs could be improved by testing collections of enzymes obtained, for instance, from metagenome search. [44] We then turned our attention to the optimization of the chemical step of the cascade using 2 a, 3 a and 4 a as model substrates (Scheme 1). It is known that the Ugi-reaction can be carried out in water making it potentially compatible with the MAO oxidation.…”

Section: Resultsmentioning

confidence: 99%

“…Amines with chloro ( 1 i – k ), fluoro ( 1 h ), methyl‐carbamoyl ( 1 l ), methyl carboxylate ( 1 u ) substituents as well as heteroaromatic analogues ( 1 m – o ) were oxidized with moderate to good conversion highlighting the synthetic utility of MAOs. As a future direction, the substrate scope and activity of MAOs could be improved by testing collections of enzymes obtained, for instance, from metagenome search [44] …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

et al. 2022

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In memory of Ferenc FülöpA one-pot two-step chemo-enzymatic approach for the functionalization of substituted 1,2,3,4-tetrahydroisoquinolines (THIQs) was developed. The system combines monoamine oxidase (MAO)-catalyzed imine formation with Ugi-type threecomponent reaction in an aqueous buffer without intermediate isolation. The two steps were separately optimized for buffer and pH to obtain the expected products. MAOs enabled the functionalization of fifteen THIQs by oxidation to imines, while the Ugi-Joullié-reaction was successfully carried out with eight carboxylic acids and eight isonitriles. 41 products were isolated giving access to valuable building blocks for medicinal chemistry applications. Gram-scale transformation demonstrated the utility of the described protocol for organic synthesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

et al. 2022

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“…In addition, fosmid libraries allow studying many complete genes that are not fully captured in metagenomic libraries. On the other hand, shotgun metagenomics is less labour-intensive, yields sequencing data faster than fosmid libraries and avoids common biases introduced through PCR-or activity-guided functional metagenomics workflows [43]. In the present study, the use of fosmid libraries allowed the identification of novel acetyltransferase and deacetylase enzymes from the microbial dark matter fraction.…”

Section: Functional Analysis Of Bile Metagenome: Metagenomic Dark Mattermentioning

confidence: 86%

Functional Characterisation of Bile Metagenome: Study of Metagenomic Dark Matter

et al. 2021

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Gallbladder metagenome involves a wide range of unidentified sequences comprising the so-called metagenomic dark matter. Therefore, this study aimed to characterise three gallbladder metagenomes and a fosmid library with an emphasis on metagenomic dark matter fraction. For this purpose, a novel data analysis strategy based on the combination of remote homology and molecular modelling has been proposed. According to the results obtained, several protein functional domains were annotated in the metagenomic dark matter fraction including acetyltransferases, outer membrane transporter proteins, membrane assembly factors, DNA repair and recombination proteins and response regulator phosphatases. In addition, one deacetylase involved in mycothiol biosynthesis was found in the metagenomic dark matter fraction of the fosmid library. This enzyme may exert a protective effect in Actinobacteria against bile components exposure, in agreement with the presence of multiple antibiotic and multidrug resistance genes. Potential mechanisms of action of this novel deacetylase were elucidated by molecular simulations, highlighting the role of histidine and aspartic acid residues. Computational pipelines presented in this work may be of special interest to discover novel microbial enzymes which had not been previously characterised.

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“…Metagenomic sequence data are a valuable source of sequence information that started to be used in protein structure prediction since a seminal article [60] and is now also extensively used in enzyme discovery [61]. For example, most methods used such information as input in the last round of the CASP experiment (CASP14) [60].…”

Section: Metagenomic Datamentioning

confidence: 99%

Artificial intelligence challenges for predicting the impact of mutations on protein stability

Pucci

Schwersensky

Rooman

2022

Current Opinion in Structural Biology

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A roadmap for metagenomic enzyme discovery

Abstract: Shotgun metagenomic approaches to uncover new enzymes are underdeveloped relative to PCR- or activity-based functional metagenomics. Here we review computational and experimental strategies to discover biosynthetic enzymes from metagenomes.

Cited by 100 publications

References 303 publications

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

Functional Characterisation of Bile Metagenome: Study of Metagenomic Dark Matter

Artificial intelligence challenges for predicting the impact of mutations on protein stability

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