Regulation of penicillin biosynthesis in filamentous fungi.

Axel A. Brakhage, Petra Spröte, Qusai Al-Abdallah, Alexander Gehrke, Hans Plattner, André Tüncher

Research output: Contribution to journalReview article

74 Citations (Scopus)

Abstract

The beta-lactam antibiotic penicillin is one of the mainly used antibiotics for the therapy of infectious diseases. It is produced as end product by some filamentous fungi only, most notably by Aspergillus (Emericella) nidulans and Penicillium chrysogenum. The penicillin biosynthesis is catalysed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aatA (penDE). The genes are organised into a gene cluster. Although the production of secondary metabolites as penicillin is not essential for the direct survival of the producing organisms, several studies indicated that the penicillin biosynthesis genes are controlled by a complex regulatory network, e.g. by the ambient pH, carbon source, amino acids, nitrogen etc. A comparison with the regulatory mechanisms (regulatory proteins and DNA elements) involved in the regulation of genes of primary metabolism in lower eukaryotes is thus of great interest. This has already led to the elucidation of new regulatory mechanisms. Positively acting regulators have been identified such as the pH dependent transcriptional regulator PACC, the CCAAT-binding complex AnCF and seem also to be represented by recessive trans-acting mutations of A. nidulans (prgA1, prgB1, npeE1) and R chrysogenum (carried by mutants Npe2 and Npe3). In addition, repressors like AnBH1 and VeA are involved in the regulation. Furthermore, such investigations have contributed to the elucidation of signals leading to the production of penicillin and can be expected to have a major impact on rational strain improvement programs.

Original languageEnglish (US)
Pages (from-to)45-90
Number of pages46
JournalAdvances in Biochemical Engineering/Biotechnology
Volume88
StatePublished - 2004
Externally publishedYes

Fingerprint

Biosynthesis
Fungi
Penicillins
Genes
Antibiotics
Emericella
Penicillium chrysogenum
Aspergillus nidulans
Aspergillus
beta-Lactams
Multigene Family
Metabolites
Eukaryota
Metabolism
Communicable Diseases
Amino acids
DNA
Nitrogen
Carbon
Enzymes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Brakhage, A. A., Spröte, P., Al-Abdallah, Q., Gehrke, A., Plattner, H., & Tüncher, A. (2004). Regulation of penicillin biosynthesis in filamentous fungi. Advances in Biochemical Engineering/Biotechnology, 88, 45-90.

Regulation of penicillin biosynthesis in filamentous fungi. / Brakhage, Axel A.; Spröte, Petra; Al-Abdallah, Qusai; Gehrke, Alexander; Plattner, Hans; Tüncher, André.

In: Advances in Biochemical Engineering/Biotechnology, Vol. 88, 2004, p. 45-90.

Research output: Contribution to journalReview article

Brakhage, AA, Spröte, P, Al-Abdallah, Q, Gehrke, A, Plattner, H & Tüncher, A 2004, 'Regulation of penicillin biosynthesis in filamentous fungi.', Advances in Biochemical Engineering/Biotechnology, vol. 88, pp. 45-90.
Brakhage, Axel A. ; Spröte, Petra ; Al-Abdallah, Qusai ; Gehrke, Alexander ; Plattner, Hans ; Tüncher, André. / Regulation of penicillin biosynthesis in filamentous fungi. In: Advances in Biochemical Engineering/Biotechnology. 2004 ; Vol. 88. pp. 45-90.
@article{f77fbf94d5614979a11eca697fb08a0f,
title = "Regulation of penicillin biosynthesis in filamentous fungi.",
abstract = "The beta-lactam antibiotic penicillin is one of the mainly used antibiotics for the therapy of infectious diseases. It is produced as end product by some filamentous fungi only, most notably by Aspergillus (Emericella) nidulans and Penicillium chrysogenum. The penicillin biosynthesis is catalysed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aatA (penDE). The genes are organised into a gene cluster. Although the production of secondary metabolites as penicillin is not essential for the direct survival of the producing organisms, several studies indicated that the penicillin biosynthesis genes are controlled by a complex regulatory network, e.g. by the ambient pH, carbon source, amino acids, nitrogen etc. A comparison with the regulatory mechanisms (regulatory proteins and DNA elements) involved in the regulation of genes of primary metabolism in lower eukaryotes is thus of great interest. This has already led to the elucidation of new regulatory mechanisms. Positively acting regulators have been identified such as the pH dependent transcriptional regulator PACC, the CCAAT-binding complex AnCF and seem also to be represented by recessive trans-acting mutations of A. nidulans (prgA1, prgB1, npeE1) and R chrysogenum (carried by mutants Npe2 and Npe3). In addition, repressors like AnBH1 and VeA are involved in the regulation. Furthermore, such investigations have contributed to the elucidation of signals leading to the production of penicillin and can be expected to have a major impact on rational strain improvement programs.",
author = "Brakhage, {Axel A.} and Petra Spr{\"o}te and Qusai Al-Abdallah and Alexander Gehrke and Hans Plattner and Andr{\'e} T{\"u}ncher",
year = "2004",
language = "English (US)",
volume = "88",
pages = "45--90",
journal = "Advances in Biochemical Engineering/Biotechnology",
issn = "0724-6145",
publisher = "Springer Science and Business Media Deutschland GmbH",

}

TY - JOUR

T1 - Regulation of penicillin biosynthesis in filamentous fungi.

AU - Brakhage, Axel A.

AU - Spröte, Petra

AU - Al-Abdallah, Qusai

AU - Gehrke, Alexander

AU - Plattner, Hans

AU - Tüncher, André

PY - 2004

Y1 - 2004

N2 - The beta-lactam antibiotic penicillin is one of the mainly used antibiotics for the therapy of infectious diseases. It is produced as end product by some filamentous fungi only, most notably by Aspergillus (Emericella) nidulans and Penicillium chrysogenum. The penicillin biosynthesis is catalysed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aatA (penDE). The genes are organised into a gene cluster. Although the production of secondary metabolites as penicillin is not essential for the direct survival of the producing organisms, several studies indicated that the penicillin biosynthesis genes are controlled by a complex regulatory network, e.g. by the ambient pH, carbon source, amino acids, nitrogen etc. A comparison with the regulatory mechanisms (regulatory proteins and DNA elements) involved in the regulation of genes of primary metabolism in lower eukaryotes is thus of great interest. This has already led to the elucidation of new regulatory mechanisms. Positively acting regulators have been identified such as the pH dependent transcriptional regulator PACC, the CCAAT-binding complex AnCF and seem also to be represented by recessive trans-acting mutations of A. nidulans (prgA1, prgB1, npeE1) and R chrysogenum (carried by mutants Npe2 and Npe3). In addition, repressors like AnBH1 and VeA are involved in the regulation. Furthermore, such investigations have contributed to the elucidation of signals leading to the production of penicillin and can be expected to have a major impact on rational strain improvement programs.

AB - The beta-lactam antibiotic penicillin is one of the mainly used antibiotics for the therapy of infectious diseases. It is produced as end product by some filamentous fungi only, most notably by Aspergillus (Emericella) nidulans and Penicillium chrysogenum. The penicillin biosynthesis is catalysed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aatA (penDE). The genes are organised into a gene cluster. Although the production of secondary metabolites as penicillin is not essential for the direct survival of the producing organisms, several studies indicated that the penicillin biosynthesis genes are controlled by a complex regulatory network, e.g. by the ambient pH, carbon source, amino acids, nitrogen etc. A comparison with the regulatory mechanisms (regulatory proteins and DNA elements) involved in the regulation of genes of primary metabolism in lower eukaryotes is thus of great interest. This has already led to the elucidation of new regulatory mechanisms. Positively acting regulators have been identified such as the pH dependent transcriptional regulator PACC, the CCAAT-binding complex AnCF and seem also to be represented by recessive trans-acting mutations of A. nidulans (prgA1, prgB1, npeE1) and R chrysogenum (carried by mutants Npe2 and Npe3). In addition, repressors like AnBH1 and VeA are involved in the regulation. Furthermore, such investigations have contributed to the elucidation of signals leading to the production of penicillin and can be expected to have a major impact on rational strain improvement programs.

UR - http://www.scopus.com/inward/record.url?scp=14744278110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14744278110&partnerID=8YFLogxK

M3 - Review article

VL - 88

SP - 45

EP - 90

JO - Advances in Biochemical Engineering/Biotechnology

JF - Advances in Biochemical Engineering/Biotechnology

SN - 0724-6145

ER -