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Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis

Non-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure–function relationship. AusE from Aspergillus nidulans and PrhA from Penicilliu... Full description

Journal Title: Nat Commun 2018, Vol.9(1), pp.104-104
Main Author: Nakashima, Yu
Other Authors: Mori, Takahiro , Nakamura, Hitomi , Awakawa, Takayoshi , Hoshino, Shotaro , Senda, Miki , Senda, Toshiya , Abe, Ikuro
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 2041-1723 ; DOI: 10.1038/s41467-017-02371-w
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recordid: palgrave_j10.1038/s41467-017-02371-w
title: Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis
format: Article
creator:
  • Nakashima, Yu
  • Mori, Takahiro
  • Nakamura, Hitomi
  • Awakawa, Takayoshi
  • Hoshino, Shotaro
  • Senda, Miki
  • Senda, Toshiya
  • Abe, Ikuro
subjects:
  • Aspergillus Nidulans -- Metabolism
  • Ketoglutaric Acids -- Chemistry
  • Mixed Function Oxygenases -- Metabolism
  • Nonheme Iron Proteins -- Chemistry
  • Penicillium -- Metabolism
  • Terpenes -- Metabolism
ispartof: Nat Commun, 2018, Vol.9(1), pp.104-104
description: Non-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure–function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/αKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/αKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
language: eng
source:
identifier: ISSN: 2041-1723 ; DOI: 10.1038/s41467-017-02371-w
fulltext: fulltext
issn:
  • 2041-1723
  • 20411723
url: Link


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titleStructure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis
creatorNakashima, Yu ; Mori, Takahiro ; Nakamura, Hitomi ; Awakawa, Takayoshi ; Hoshino, Shotaro ; Senda, Miki ; Senda, Toshiya ; Abe, Ikuro
ispartofNat Commun, 2018, Vol.9(1), pp.104-104
identifierISSN: 2041-1723 ; DOI: 10.1038/s41467-017-02371-w
descriptionNon-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure–function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/αKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/αKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
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subjectAspergillus Nidulans -- Metabolism ; Ketoglutaric Acids -- Chemistry ; Mixed Function Oxygenases -- Metabolism ; Nonheme Iron Proteins -- Chemistry ; Penicillium -- Metabolism ; Terpenes -- Metabolism;
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titleStructure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis
descriptionNon-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure–function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/αKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/αKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
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abstractNon-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure–function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/αKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/αKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
pubNature Publishing Group UK
doi10.1038/s41467-017-02371-w
pages104
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