Molecular mechanism of polyketide shortening in anthraquinone biosynthesis of: Photorhabdus luminescens

Qiuqin Zhou; Alois Bräuer; Hélène Adihou; Maximilian Schmalhofer; Patricia Saura; Gina L.C. Grammbitter; Ville R.I. Kaila; Michael Groll; Helge B. Bode

doi:10.1039/c9sc00749k

Molecular mechanism of polyketide shortening in anthraquinone biosynthesis of: Photorhabdus luminescens

Qiuqin Zhou, Alois Bräuer, Hélène Adihou, Maximilian Schmalhofer, Patricia Saura, Gina L.C. Grammbitter, Ville R.I. Kaila, Michael Groll, Helge B. Bode

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Abstract

Anthraquinones, a widely distributed class of aromatic natural products, are produced by a type II polyketide synthase system in the Gram-negative bacterium Photorhabdus luminescens. Heterologous expression of the antABCDEFGHI anthraquinone biosynthetic gene cluster in Escherichia coli identified AntI as an unusual lyase, catalysing terminal polyketide shortening prior to formation of the third aromatic ring. Functional in vitro and in vivo analysis of AntI using X-ray crystallography, structure-based mutagenesis, and molecular simulations revealed that AntI converts a defined octaketide to the tricyclic anthraquinone ring via retro-Claisen and Dieckmann reactions. Thus, AntI catalyses a so far unobserved multistep reaction in this PKS system.

Original language	English
Pages (from-to)	6341-6349
Number of pages	9
Journal	Chemical Science
Volume	10
Issue number	25
DOIs	https://doi.org/10.1039/c9sc00749k
State	Published - 2019

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title = "Molecular mechanism of polyketide shortening in anthraquinone biosynthesis of: Photorhabdus luminescens",

abstract = "Anthraquinones, a widely distributed class of aromatic natural products, are produced by a type II polyketide synthase system in the Gram-negative bacterium Photorhabdus luminescens. Heterologous expression of the antABCDEFGHI anthraquinone biosynthetic gene cluster in Escherichia coli identified AntI as an unusual lyase, catalysing terminal polyketide shortening prior to formation of the third aromatic ring. Functional in vitro and in vivo analysis of AntI using X-ray crystallography, structure-based mutagenesis, and molecular simulations revealed that AntI converts a defined octaketide to the tricyclic anthraquinone ring via retro-Claisen and Dieckmann reactions. Thus, AntI catalyses a so far unobserved multistep reaction in this PKS system.",

author = "Qiuqin Zhou and Alois Br{\"a}uer and H{\'e}l{\`e}ne Adihou and Maximilian Schmalhofer and Patricia Saura and Grammbitter, {Gina L.C.} and Kaila, {Ville R.I.} and Michael Groll and Bode, {Helge B.}",

note = "Publisher Copyright: {\textcopyright} 2019 The Royal Society of Chemistry.",

year = "2019",

doi = "10.1039/c9sc00749k",

language = "English",

volume = "10",

pages = "6341--6349",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Molecular mechanism of polyketide shortening in anthraquinone biosynthesis of

T2 - Photorhabdus luminescens

AU - Zhou, Qiuqin

AU - Bräuer, Alois

AU - Adihou, Hélène

AU - Schmalhofer, Maximilian

AU - Saura, Patricia

AU - Grammbitter, Gina L.C.

AU - Kaila, Ville R.I.

AU - Groll, Michael

AU - Bode, Helge B.

PY - 2019

Y1 - 2019

N2 - Anthraquinones, a widely distributed class of aromatic natural products, are produced by a type II polyketide synthase system in the Gram-negative bacterium Photorhabdus luminescens. Heterologous expression of the antABCDEFGHI anthraquinone biosynthetic gene cluster in Escherichia coli identified AntI as an unusual lyase, catalysing terminal polyketide shortening prior to formation of the third aromatic ring. Functional in vitro and in vivo analysis of AntI using X-ray crystallography, structure-based mutagenesis, and molecular simulations revealed that AntI converts a defined octaketide to the tricyclic anthraquinone ring via retro-Claisen and Dieckmann reactions. Thus, AntI catalyses a so far unobserved multistep reaction in this PKS system.

AB - Anthraquinones, a widely distributed class of aromatic natural products, are produced by a type II polyketide synthase system in the Gram-negative bacterium Photorhabdus luminescens. Heterologous expression of the antABCDEFGHI anthraquinone biosynthetic gene cluster in Escherichia coli identified AntI as an unusual lyase, catalysing terminal polyketide shortening prior to formation of the third aromatic ring. Functional in vitro and in vivo analysis of AntI using X-ray crystallography, structure-based mutagenesis, and molecular simulations revealed that AntI converts a defined octaketide to the tricyclic anthraquinone ring via retro-Claisen and Dieckmann reactions. Thus, AntI catalyses a so far unobserved multistep reaction in this PKS system.

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U2 - 10.1039/c9sc00749k

DO - 10.1039/c9sc00749k

M3 - Article

AN - SCOPUS:85068118844

SN - 2041-6520

VL - 10

SP - 6341

EP - 6349

JO - Chemical Science

JF - Chemical Science

IS - 25

ER -

Molecular mechanism of polyketide shortening in anthraquinone biosynthesis of: Photorhabdus luminescens

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