Publication

Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase

Weber, S. S., Polli, F., Boer, R., Bovenberg, R. A. L. & Driessen, A. J. M., Oct-2012, In : Applied and environmental microbiology. 78, 19, p. 7107-7113 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Weber, S. S., Polli, F., Boer, R., Bovenberg, R. A. L., & Driessen, A. J. M. (2012). Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase. Applied and environmental microbiology, 78(19), 7107-7113. https://doi.org/10.1128/AEM.01529-12

Author

Weber, Stefan S. ; Polli, Fabiola ; Boer, Remon ; Bovenberg, Roel A. L. ; Driessen, Arnold J. M. / Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase. In: Applied and environmental microbiology. 2012 ; Vol. 78, No. 19. pp. 7107-7113.

Harvard

Weber, SS, Polli, F, Boer, R, Bovenberg, RAL & Driessen, AJM 2012, 'Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase', Applied and environmental microbiology, vol. 78, no. 19, pp. 7107-7113. https://doi.org/10.1128/AEM.01529-12

Standard

Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase. / Weber, Stefan S.; Polli, Fabiola; Boer, Remon; Bovenberg, Roel A. L.; Driessen, Arnold J. M.

In: Applied and environmental microbiology, Vol. 78, No. 19, 10.2012, p. 7107-7113.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Weber SS, Polli F, Boer R, Bovenberg RAL, Driessen AJM. Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase. Applied and environmental microbiology. 2012 Oct;78(19):7107-7113. https://doi.org/10.1128/AEM.01529-12


BibTeX

@article{a1fe8fc36a884686a2262b58b0367908,
title = "Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase",
abstract = "Intense classical strain improvement has yielded industrial Penicillium chrysogenum strains that produce high titers of penicillin. These strains contain multiple copies of the penicillin biosynthesis cluster encoding the three key enzymes: delta-(l-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthase (IPNS), and isopenicillin N acyltransferase (IAT). The phenylacetic acid coenzyme A (CoA) ligase (PCL) gene encoding the enzyme responsible for the activation of the side chain precursor phenylacetic acid is localized elsewhere in the genome in a single copy. Since the protein level of IAT already saturates at low cluster copy numbers, IAT might catalyze a limiting step in high-yielding strains. Here, we show that penicillin production in high-yielding strains can be further improved by the overexpression of IAT while at very high levels of IAT the precursor 6-aminopenicillic acid (6-APA) accumulates. Overproduction of PCL only marginally stimulates penicillin production. These data demonstrate that in high-yielding strains IAT is the limiting factor and that this limitation can be alleviated by a balanced overproduction of this enzyme.",
keywords = "GENE-CLUSTER, ASPERGILLUS-NIDULANS, ACID ACYLTRANSFERASE, PHENYLACETIC ACID, BIOSYNTHESIS, AMPLIFICATION, CEPHALOSPORIN, ORGANIZATION, ANTIBIOTICS, SYSTEM",
author = "Weber, {Stefan S.} and Fabiola Polli and Remon Boer and Bovenberg, {Roel A. L.} and Driessen, {Arnold J. M.}",
year = "2012",
month = oct,
doi = "10.1128/AEM.01529-12",
language = "English",
volume = "78",
pages = "7107--7113",
journal = "Applied Environmental Microbiology",
issn = "0099-2240",
publisher = "AMER SOC MICROBIOLOGY",
number = "19",

}

RIS

TY - JOUR

T1 - Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase

AU - Weber, Stefan S.

AU - Polli, Fabiola

AU - Boer, Remon

AU - Bovenberg, Roel A. L.

AU - Driessen, Arnold J. M.

PY - 2012/10

Y1 - 2012/10

N2 - Intense classical strain improvement has yielded industrial Penicillium chrysogenum strains that produce high titers of penicillin. These strains contain multiple copies of the penicillin biosynthesis cluster encoding the three key enzymes: delta-(l-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthase (IPNS), and isopenicillin N acyltransferase (IAT). The phenylacetic acid coenzyme A (CoA) ligase (PCL) gene encoding the enzyme responsible for the activation of the side chain precursor phenylacetic acid is localized elsewhere in the genome in a single copy. Since the protein level of IAT already saturates at low cluster copy numbers, IAT might catalyze a limiting step in high-yielding strains. Here, we show that penicillin production in high-yielding strains can be further improved by the overexpression of IAT while at very high levels of IAT the precursor 6-aminopenicillic acid (6-APA) accumulates. Overproduction of PCL only marginally stimulates penicillin production. These data demonstrate that in high-yielding strains IAT is the limiting factor and that this limitation can be alleviated by a balanced overproduction of this enzyme.

AB - Intense classical strain improvement has yielded industrial Penicillium chrysogenum strains that produce high titers of penicillin. These strains contain multiple copies of the penicillin biosynthesis cluster encoding the three key enzymes: delta-(l-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthase (IPNS), and isopenicillin N acyltransferase (IAT). The phenylacetic acid coenzyme A (CoA) ligase (PCL) gene encoding the enzyme responsible for the activation of the side chain precursor phenylacetic acid is localized elsewhere in the genome in a single copy. Since the protein level of IAT already saturates at low cluster copy numbers, IAT might catalyze a limiting step in high-yielding strains. Here, we show that penicillin production in high-yielding strains can be further improved by the overexpression of IAT while at very high levels of IAT the precursor 6-aminopenicillic acid (6-APA) accumulates. Overproduction of PCL only marginally stimulates penicillin production. These data demonstrate that in high-yielding strains IAT is the limiting factor and that this limitation can be alleviated by a balanced overproduction of this enzyme.

KW - GENE-CLUSTER

KW - ASPERGILLUS-NIDULANS

KW - ACID ACYLTRANSFERASE

KW - PHENYLACETIC ACID

KW - BIOSYNTHESIS

KW - AMPLIFICATION

KW - CEPHALOSPORIN

KW - ORGANIZATION

KW - ANTIBIOTICS

KW - SYSTEM

U2 - 10.1128/AEM.01529-12

DO - 10.1128/AEM.01529-12

M3 - Article

VL - 78

SP - 7107

EP - 7113

JO - Applied Environmental Microbiology

JF - Applied Environmental Microbiology

SN - 0099-2240

IS - 19

ER -

ID: 5665550