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Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides

Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide... Full description

Journal Title: Angewandte Chemie 06 February 2017, Vol.129(7), pp.1766-1771
Main Author: Zhang, Lihan
Other Authors: Hashimoto, Takuya , Qin, Bin , Hashimoto, Junko , Kozone, Ikuko , Kawahara, Teppei , Okada, Masahiro , Awakawa, Takayoshi , Ito, Takuya , Asakawa, Yoshinori , Ueki, Masashi , Takahashi, Shunji , Osada, Hiroyuki , Wakimoto, Toshiyuki , Ikeda, Haruo , Shin‐Ya, Kazuo , Abe, Ikuro
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0044-8249 ; E-ISSN: 1521-3757 ; DOI: 10.1002/ange.201611371
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title: Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
format: Article
creator:
  • Zhang, Lihan
  • Hashimoto, Takuya
  • Qin, Bin
  • Hashimoto, Junko
  • Kozone, Ikuko
  • Kawahara, Teppei
  • Okada, Masahiro
  • Awakawa, Takayoshi
  • Ito, Takuya
  • Asakawa, Yoshinori
  • Ueki, Masashi
  • Takahashi, Shunji
  • Osada, Hiroyuki
  • Wakimoto, Toshiyuki
  • Ikeda, Haruo
  • Shin‐Ya, Kazuo
  • Abe, Ikuro
subjects:
  • Bioengineering
  • Biosynthese
  • Polyketide
  • Proteinstrukturen
ispartof: Angewandte Chemie, 06 February 2017, Vol.129(7), pp.1766-1771
description: Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide synthases (PKSs) responsible for the production of aminopolyol polyketides. Heterologous expression of over 150 kbp polyketide gene clusters successfully afforded their products, whose stereochemistry was established by taking advantage of bioinformatic analysis. Furthermore, phylogenetic analysis of highly homologous but functionally diverse domains from the giant PKSs demonstrated the evolutionary mechanism for structural diversification of polyketides. The gene clusters characterized herein, together with their evolutionary insights, are promising genetic building blocks for de novo production of unnatural polyketides. : Aminopolyole sind eine Klasse von bioaktiven Polyketiden, die durch große modulare Polyketidsynthasen (PKSs) aufgebaut werden. Die heterologe Expression von PKS‐Genclustern mit über 150 kbp führte zu neuartigen Aminopolyolen, und ein phylogenetischer Vergleich von vier Aminopolyol‐PKS‐Genclustern veranschaulicht den präzisen Mechanismus der PKS‐Umprogrammierung in der Natur.
language: eng
source:
identifier: ISSN: 0044-8249 ; E-ISSN: 1521-3757 ; DOI: 10.1002/ange.201611371
fulltext: fulltext
issn:
  • 0044-8249
  • 00448249
  • 1521-3757
  • 15213757
url: Link


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titleCharacterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
creatorZhang, Lihan ; Hashimoto, Takuya ; Qin, Bin ; Hashimoto, Junko ; Kozone, Ikuko ; Kawahara, Teppei ; Okada, Masahiro ; Awakawa, Takayoshi ; Ito, Takuya ; Asakawa, Yoshinori ; Ueki, Masashi ; Takahashi, Shunji ; Osada, Hiroyuki ; Wakimoto, Toshiyuki ; Ikeda, Haruo ; Shin‐Ya, Kazuo ; Abe, Ikuro
ispartofAngewandte Chemie, 06 February 2017, Vol.129(7), pp.1766-1771
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subjectBioengineering ; Biosynthese ; Polyketide ; Proteinstrukturen
descriptionPolyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide synthases (PKSs) responsible for the production of aminopolyol polyketides. Heterologous expression of over 150 kbp polyketide gene clusters successfully afforded their products, whose stereochemistry was established by taking advantage of bioinformatic analysis. Furthermore, phylogenetic analysis of highly homologous but functionally diverse domains from the giant PKSs demonstrated the evolutionary mechanism for structural diversification of polyketides. The gene clusters characterized herein, together with their evolutionary insights, are promising genetic building blocks for de novo production of unnatural polyketides. : Aminopolyole sind eine Klasse von bioaktiven Polyketiden, die durch große modulare Polyketidsynthasen (PKSs) aufgebaut werden. Die heterologe Expression von PKS‐Genclustern mit über 150 kbp führte zu neuartigen Aminopolyolen, und ein phylogenetischer Vergleich von vier Aminopolyol‐PKS‐Genclustern veranschaulicht den präzisen Mechanismus der PKS‐Umprogrammierung in der Natur.
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titleCharacterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
descriptionPolyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide synthases (PKSs) responsible for the production of aminopolyol polyketides. Heterologous expression of over 150 kbp polyketide gene clusters successfully afforded their products, whose stereochemistry was established by taking advantage of bioinformatic analysis. Furthermore, phylogenetic analysis of highly homologous but functionally diverse domains from the giant PKSs demonstrated the evolutionary mechanism for structural diversification of polyketides. The gene clusters characterized herein, together with their evolutionary insights, are promising genetic building blocks for de novo production of unnatural polyketides. : Aminopolyole sind eine Klasse von bioaktiven Polyketiden, die durch große modulare Polyketidsynthasen (PKSs) aufgebaut werden. Die heterologe Expression von PKS‐Genclustern mit über 150 kbp führte zu neuartigen Aminopolyolen, und ein phylogenetischer Vergleich von vier Aminopolyol‐PKS‐Genclustern veranschaulicht den präzisen Mechanismus der PKS‐Umprogrammierung in der Natur.
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titleCharacterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides
authorZhang, Lihan ; Hashimoto, Takuya ; Qin, Bin ; Hashimoto, Junko ; Kozone, Ikuko ; Kawahara, Teppei ; Okada, Masahiro ; Awakawa, Takayoshi ; Ito, Takuya ; Asakawa, Yoshinori ; Ueki, Masashi ; Takahashi, Shunji ; Osada, Hiroyuki ; Wakimoto, Toshiyuki ; Ikeda, Haruo ; Shin‐Ya, Kazuo ; Abe, Ikuro
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abstractPolyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery. Herein, we report characterization of giant modular polyketide synthases (PKSs) responsible for the production of aminopolyol polyketides. Heterologous expression of over 150 kbp polyketide gene clusters successfully afforded their products, whose stereochemistry was established by taking advantage of bioinformatic analysis. Furthermore, phylogenetic analysis of highly homologous but functionally diverse domains from the giant PKSs demonstrated the evolutionary mechanism for structural diversification of polyketides. The gene clusters characterized herein, together with their evolutionary insights, are promising genetic building blocks for de novo production of unnatural polyketides. : Aminopolyole sind eine Klasse von bioaktiven Polyketiden, die durch große modulare Polyketidsynthasen (PKSs) aufgebaut werden. Die heterologe Expression von PKS‐Genclustern mit über 150 kbp führte zu neuartigen Aminopolyolen, und ein phylogenetischer Vergleich von vier Aminopolyol‐PKS‐Genclustern veranschaulicht den präzisen Mechanismus der PKS‐Umprogrammierung in der Natur.
doi10.1002/ange.201611371
orcididhttp://orcid.org/0000-0002-3640-888X
pages1766-1771
date2017-02-06