Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis

Ahmed al Fahad; Amira Abood; Katja M. Fisch; Anna Osipow; Jack Davison; Marija Avramovic; Craig P. Butts; Joern Piel; Thomas J. Simpson; Russell J. Cox

doi:10.1039/c3sc52911h

Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis

Ahmed al Fahad, Amira Abood, Katja M. Fisch, Anna Osipow, Jack Davison, Marija Avramovic, Craig P. Butts, Joern Piel, Thomas J. Simpson, Russell J. Cox^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

70 Citations (Scopus)

Abstract

An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The enzyme efficiently performed the oxidative dearomatisation of sorbicillin and dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively. Bioinformatic examination of the gene cluster surrounding SorbC indicated the presence of two polyketide synthase (PKS) encoding genes designated sorbA and sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes a non-reducing iterative PKS which features a reductive release domain usually involved in the production of polyketide aldehydes. Using these observations and previously reported results from isotopic feeding experiments a new and simpler biosynthetic route to the sorbicillin class of secondary metabolites is proposed which is consistent with all reported experimental results.

Original language	English
Pages (from-to)	523-527
Number of pages	5
Journal	Chemical Science
Volume	5
Issue number	2
DOIs	https://doi.org/10.1039/c3sc52911h
Publication status	Published - 2014

Keywords

POLYKETIDE SYNTHASE GENES
TRICHODERMA SP USF-2690
PENICILLIUM-CHRYSOGENUM
VERTICILLIUM-INTERTEXTUM
ASPERGILLUS-NIDULANS
FUNGAL POLYKETIDE
GIBBERELLA-ZEAE
CLUSTER
PATHWAY
SORBICILLACTONE

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3-month Core Capability for Chemistry Research
Crosby, J. (Principal Investigator)
1/01/13 → 1/04/13
Project: Research
Understanding Programming in Highly Reducing Iterative Fungal Polyketide Synthases - a Structural and Mechanistic Approach
Simpson, T. J. (Principal Investigator)
1/07/11 → 1/01/15
Project: Research
CHEMICAL ANALYSIS OF HYBRID FUNGAL MEGASYNTHASES
Cox, R. J. (Principal Investigator)
1/10/08 → 1/10/12
Project: Research

Professor Craig P Butts
- Craig.Buttsbristol.acuk
- School of Chemistry - Head of School, Professor of Structural and Mechanistic Chemistry
Person: Academic , Professional and Administrative

Cite this

@article{41b3b6e0db714e6c980c8712d6d03c78,

title = "Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis",

abstract = "An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The enzyme efficiently performed the oxidative dearomatisation of sorbicillin and dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively. Bioinformatic examination of the gene cluster surrounding SorbC indicated the presence of two polyketide synthase (PKS) encoding genes designated sorbA and sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes a non-reducing iterative PKS which features a reductive release domain usually involved in the production of polyketide aldehydes. Using these observations and previously reported results from isotopic feeding experiments a new and simpler biosynthetic route to the sorbicillin class of secondary metabolites is proposed which is consistent with all reported experimental results.",

keywords = "POLYKETIDE SYNTHASE GENES, TRICHODERMA SP USF-2690, PENICILLIUM-CHRYSOGENUM, VERTICILLIUM-INTERTEXTUM, ASPERGILLUS-NIDULANS, FUNGAL POLYKETIDE, GIBBERELLA-ZEAE, CLUSTER, PATHWAY, SORBICILLACTONE",

author = "{al Fahad}, Ahmed and Amira Abood and Fisch, {Katja M.} and Anna Osipow and Jack Davison and Marija Avramovic and Butts, {Craig P.} and Joern Piel and Simpson, {Thomas J.} and Cox, {Russell J.}",

year = "2014",

doi = "10.1039/c3sc52911h",

language = "English",

volume = "5",

pages = "523--527",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

number = "2",

}

TY - JOUR

T1 - Oxidative dearomatisation

T2 - the key step of sorbicillinoid biosynthesis

AU - al Fahad, Ahmed

AU - Abood, Amira

AU - Fisch, Katja M.

AU - Osipow, Anna

AU - Davison, Jack

AU - Avramovic, Marija

AU - Butts, Craig P.

AU - Piel, Joern

AU - Simpson, Thomas J.

AU - Cox, Russell J.

PY - 2014

Y1 - 2014

N2 - An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The enzyme efficiently performed the oxidative dearomatisation of sorbicillin and dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively. Bioinformatic examination of the gene cluster surrounding SorbC indicated the presence of two polyketide synthase (PKS) encoding genes designated sorbA and sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes a non-reducing iterative PKS which features a reductive release domain usually involved in the production of polyketide aldehydes. Using these observations and previously reported results from isotopic feeding experiments a new and simpler biosynthetic route to the sorbicillin class of secondary metabolites is proposed which is consistent with all reported experimental results.

AB - An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The enzyme efficiently performed the oxidative dearomatisation of sorbicillin and dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively. Bioinformatic examination of the gene cluster surrounding SorbC indicated the presence of two polyketide synthase (PKS) encoding genes designated sorbA and sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes a non-reducing iterative PKS which features a reductive release domain usually involved in the production of polyketide aldehydes. Using these observations and previously reported results from isotopic feeding experiments a new and simpler biosynthetic route to the sorbicillin class of secondary metabolites is proposed which is consistent with all reported experimental results.

KW - POLYKETIDE SYNTHASE GENES

KW - TRICHODERMA SP USF-2690

KW - PENICILLIUM-CHRYSOGENUM

KW - VERTICILLIUM-INTERTEXTUM

KW - ASPERGILLUS-NIDULANS

KW - FUNGAL POLYKETIDE

KW - GIBBERELLA-ZEAE

KW - CLUSTER

KW - PATHWAY

KW - SORBICILLACTONE

U2 - 10.1039/c3sc52911h

DO - 10.1039/c3sc52911h

M3 - Article (Academic Journal)

C2 - 25580210

SN - 2041-6520

VL - 5

SP - 523

EP - 527

JO - Chemical Science

JF - Chemical Science

IS - 2

ER -

Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis

Abstract

Keywords

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Projects

3-month Core Capability for Chemistry Research

Understanding Programming in Highly Reducing Iterative Fungal Polyketide Synthases - a Structural and Mechanistic Approach

CHEMICAL ANALYSIS OF HYBRID FUNGAL MEGASYNTHASES

Profiles

Professor Craig P Butts

Cite this