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PMID: 9729600 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Molecular regulation of beta-lactam biosynthesis in filamentous fungi.

Microbiology and molecular biology reviews : MMBR ·Vol. 62 ·No. 3 ·1998-09-00 ·Pages 547-85

Brakhage AA

Abstract

The most commonly used beta-lactam antibiotics for the therapy of infectious diseases are penicillin and cephalosporin. Penicillin is produced as an end product by some fungi, most notably by Aspergillus (Emericella) nidulans and Penicillium chrysogenum. Cephalosporins are synthesized by both bacteria and fungi, e.g., by the fungus Acremonium chrysogenum (Cephalosporium acremonium). The biosynthetic pathways leading to both secondary metabolites start from the same three amino acid precursors and have the first two enzymatic reactions in common. Penicillin biosynthesis is catalyzed by three enzymes encoded by acvA (pcbAB), ipnA (pcbC), and aatA (penDE). The genes are organized into a cluster. In A. chrysogenum, in addition to acvA and ipnA, a second cluster contains the genes encoding enzymes that catalyze the reactions of the later steps of the cephalosporin pathway (cefEF and cefG). Within the last few years, several studies have indicated that the fungal beta-lactam biosynthesis genes are controlled by a complex regulatory network, e. g., by the ambient pH, carbon source, and amino acids. 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. Furthermore, such investigations have contributed to the elucidation of signals leading to the production of beta-lactams and their physiological meaning for the producing fungi, and they can be expected to have a major impact on rational strain improvement programs. The knowledge of biosynthesis genes has already been used to produce new compounds.

MeSH Terms
Anti-Bacterial Agents/biosynthesis Fungi/metabolism Gene Expression Regulation, Fungal/physiology Models, Chemical beta-Lactams/metabolism
Chemicals
Anti-Bacterial Agents beta-Lactams
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Brakhage A A
Lehrstuhl für Mikrobiologie, Universität München, D-80638 Munich, Germany. Brakhage@bio1.bio.tu-darmstadt.de
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Article Info
Journal
Microbiology and molecular biology reviews : MMBR
Abbr.
Microbiol Mol Biol Rev
ISSN
1092-2172
DOI
10.1128/MMBR.62.3.547-585.1998
Email
brakhage@bio1.bio.tu-darmstadt.de
Published
1998-09-00
Pages
547-85
Language
English
Region
United States
NLM ID
9706653
PMCID
PMC98925
Subset
IM
External Links
PubMed source DOI: 10.1128/MMBR.62.3.547-585.1998 PMC Full Text View journal details
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