Shift to pseudomonic acid B production in P-fluorescens NCIMB10586 by mutation of Mupirocin tailoring genes mupO, mupV, and macpE

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Shift to pseudomonic acid B production in P-fluorescens NCIMB10586 by mutation of Mupirocin tailoring genes mupO, mupV, and macpE. / Cooper, Sian; Laosripaiboon, W; Rahman, Ayesha; Hothersall, Joanne; El-Sayed, AK; Winfield, C; Crosby, J; Cox, RJ; Simpson, TJ; Thomas, Christopher.

In: Chemistry & Biology, Vol. 12, No. 7, 01.07.2005, p. 825-833.

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Cooper, Sian ; Laosripaiboon, W ; Rahman, Ayesha ; Hothersall, Joanne ; El-Sayed, AK ; Winfield, C ; Crosby, J ; Cox, RJ ; Simpson, TJ ; Thomas, Christopher. / Shift to pseudomonic acid B production in P-fluorescens NCIMB10586 by mutation of Mupirocin tailoring genes mupO, mupV, and macpE. In: Chemistry & Biology. 2005 ; Vol. 12, No. 7. pp. 825-833.

Bibtex

@article{4e091fac8f384f7e9907e12aa762e29a,
title = "Shift to pseudomonic acid B production in P-fluorescens NCIMB10586 by mutation of Mupirocin tailoring genes mupO, mupV, and macpE",
abstract = "Mupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixture of pseudomonic acids (PA) that target isoleucyl-tRNA synthase. The mup gene cluster encodes both type I polyketide synthases and monofunctional enzymes that should play a role during the conversion of the product of the polyketide synthase into the active antibiotic (tailoring). By in-frame deletion analysis of selected tailoring open-reading frames we show that mupQ, mupS, mupT, and mupW are essential for mupirocin production, whereas mupO, mupU, mupV, and macpE are essential for production of PA-A but not PA-B. Therefore, PA-B is not simply produced by hydroxylation of PA-A but is either a precursor of PA-A or a shunt product. In the mupW mutant, a new metabolite lacking the tetrahydropyran ring is produced, implicating mupW in oxidation of the 16-methyl group.",
author = "Sian Cooper and W Laosripaiboon and Ayesha Rahman and Joanne Hothersall and AK El-Sayed and C Winfield and J Crosby and RJ Cox and TJ Simpson and Christopher Thomas",
year = "2005",
month = jul
day = "1",
doi = "10.1016/j.chembiol.2005.05.015",
language = "English",
volume = "12",
pages = "825--833",
journal = "Chemistry & Biology",
issn = "1074-5521",
publisher = "Elsevier",
number = "7",

}

RIS

TY - JOUR

T1 - Shift to pseudomonic acid B production in P-fluorescens NCIMB10586 by mutation of Mupirocin tailoring genes mupO, mupV, and macpE

AU - Cooper, Sian

AU - Laosripaiboon, W

AU - Rahman, Ayesha

AU - Hothersall, Joanne

AU - El-Sayed, AK

AU - Winfield, C

AU - Crosby, J

AU - Cox, RJ

AU - Simpson, TJ

AU - Thomas, Christopher

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Mupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixture of pseudomonic acids (PA) that target isoleucyl-tRNA synthase. The mup gene cluster encodes both type I polyketide synthases and monofunctional enzymes that should play a role during the conversion of the product of the polyketide synthase into the active antibiotic (tailoring). By in-frame deletion analysis of selected tailoring open-reading frames we show that mupQ, mupS, mupT, and mupW are essential for mupirocin production, whereas mupO, mupU, mupV, and macpE are essential for production of PA-A but not PA-B. Therefore, PA-B is not simply produced by hydroxylation of PA-A but is either a precursor of PA-A or a shunt product. In the mupW mutant, a new metabolite lacking the tetrahydropyran ring is produced, implicating mupW in oxidation of the 16-methyl group.

AB - Mupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixture of pseudomonic acids (PA) that target isoleucyl-tRNA synthase. The mup gene cluster encodes both type I polyketide synthases and monofunctional enzymes that should play a role during the conversion of the product of the polyketide synthase into the active antibiotic (tailoring). By in-frame deletion analysis of selected tailoring open-reading frames we show that mupQ, mupS, mupT, and mupW are essential for mupirocin production, whereas mupO, mupU, mupV, and macpE are essential for production of PA-A but not PA-B. Therefore, PA-B is not simply produced by hydroxylation of PA-A but is either a precursor of PA-A or a shunt product. In the mupW mutant, a new metabolite lacking the tetrahydropyran ring is produced, implicating mupW in oxidation of the 16-methyl group.

UR - http://www.scopus.com/inward/record.url?scp=22544461948&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2005.05.015

DO - 10.1016/j.chembiol.2005.05.015

M3 - Article

VL - 12

SP - 825

EP - 833

JO - Chemistry & Biology

JF - Chemistry & Biology

SN - 1074-5521

IS - 7

ER -