Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins

  title={Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins},
  author={Juan Francisco Mart{\'i}n and Santiago Guti{\'e}rrez and Francisco J Fern{\'a}ndez and Javier Velasco and Francisco Fierro and Ana T Marcos and Katarina Kosalkov{\'a}},
  journal={Antonie van Leeuwenhoek},
The genespcbAB,pcbC andpenDE encoding the enzymes (α-aminoadipyl-cysteinyl-valine synthetase, isopenicillin N synthase and isopenicillin N acyltransferase, respectively) involved in the biosynthesis of penicillin have been cloned fromPenicillium chrysogenum andAspergillus nidulans. They are clustered in chromosome I (10.4 Mb) ofP. chrysogenum, in chromosome II ofPenicillium notatum (9.6 Mb) and in chromosome VI (3.0 Mb) ofA. nidulans. Each gene is expressed as a single transcript from separate… Expand
Molecular characterization of a fungal gene paralogue of the penicillin penDE gene of Penicillium chrysogenum
The data suggest that like in A. nidulans, the ial and penDE genes might have been formed from a single ancestral gene that became duplicated during evolution, although a separate evolutive origin for the IAL and pende genes, is also discussed. Expand
Cloning, expression and characterisation of the starter module from indanomycin biosynthesis
Initial investigations into holo-IdmK suggest that the phosphopantetheine co-factor is directed into the hydrophobic core of the protein, which has set up the system for future studies to engineer the pathway for novel product biosynthesis. Expand
Post-translational enzyme modification by the phosphopantetheinyl transferase is required for lysine and penicillin biosynthesis but not for roquefortine or fatty acid formation in Penicillium chrysogenum.
Complementation of Wis54-PPT(-) with the ppt gene restored lysine biosynthesis, pigmentation and penicillin production, which demonstrates the wide range of processes controlled by this gene. Expand
The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicillium chrysogenum.
Evidence is found that PcLaeA not only controls some secondary metabolism gene clusters, but also asexual differentiation in P. chrysogenum. Expand
Evolution of fungal β-lactam biosynthesis gene clusters
Filamentous fungi are microorganisms of great biotechnological interest due to their ability to synthesize a variety of bioactive secondary metabolites including β-lactam antibiotics, such asExpand
Biosynthesis and molecular genetics of cephamycins
  • P. Liras
  • Biology
  • Antonie van Leeuwenhoek
  • 2004
Cephamycin C is produced in a nine steps pathway by the actinomycetes S. clavuligerus and N. lactamdurans, a Gram negative bacterium and the genes encoding the biosynthesis enzymes are clustered in both microorganisms as well as in the cephabacin producer Lysobacter lactamgenus. Expand
The Use of Directed Evolution Towards Altering the Substrate Specificity of Acyl-Coenzyme A: Isopenicillin N Acyl Transferase and Transforming it from Generalist to Specialist
This thesis describes the identification of a AT mutant with improved acylation activity (AAT activity) via screening of an AT library using a previously developed screening method and investigates the potential of increasing the sensitivity of an assay by targeting AT to the periplasm. Expand
Advances in Beta-Lactam Antibiotics
Modern aspects of the processes are discussed in the present review including genetics, molecular biology, metabolic engineering, genomics, and proteomics, including the confined manipulation of genetically modified organisms (GMOs). Expand
Transport processes in penicillin biosynthesis
A simple model system based on isolated plasma membranes had to be constructed to study the nature and specificity of the transport systems that reside in the plasma membrane and that are of important in penicillin production. Expand
Bacterial synthesis of d-amino acids
  • A. Radkov, L. Moe
  • Biology, Medicine
  • Applied Microbiology and Biotechnology
  • 2014
The roles of d-amino acids in bacterial physiology and biotechnology are reviewed, the known mechanisms by which they are synthesized by bacteria are described, and they are proposed to foretell movement from exponential growth phase into stationary phase. Expand


Cloning and characterization of the acyl-coenzyme A: 6-aminopenicillanic-acid-acyltransferase gene of Penicillium chrysogenum.
The aat gene of P. chrysogenum resembles the genes encoding Pn acylases of Escherichia coli, Proteus rettgeri and Pseudomonas sp. Expand
Cloning and Expression of the Fungal Expandase/hydroxylase Gene Involved in Cephalosporin Biosynthesis
The cloned DAOCS/DACS gene represents an important tool for enhancing production of known cephalosporins and for synthesis of novel cep HALsporins. Expand
Two genes involved in penicillin biosynthesis are linked in a 5.1 kb SalI fragment in the genome of Penicillium chrysogenum
Two genes, pcbC and penDE, encoding the enzymes isopenicillin N synthase and acyl-CoA:6-amino penicillanic acid (6-APA) acyltransferase, which are involved in the penicillin biosynthetic pathway in Penicillium chrysogenum were cloned. Expand
Cloning, characterization of the acyl-CoA : 6-amino penicillanic acid acyltransferase gene of Aspergillus nidulans and linkage to the isopenicillin N synthase gene
SummaryThe penDE gene encoding acyl-CoA:6-amino penicillanic acid acyltransferase (AAT), the last enzyme of the penicillin biosynthetic pathway, has been cloned from the DNA of Aspergillus nidulans.Expand
Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium
The cloning, characterization and expression in Escherichia coli of the gene encoding the IPS protein in Cephalosporium acremonium is reported, and a new protein co-migrating with authentic IPS as the major protein of the cell. Expand
The cluster of penicillin biosynthetic genes. Identification and characterization of the pcbAB gene encoding the alpha-aminoadipyl-cysteinyl-valine synthetase and linkage to the pcbC and penDE genes.
Penicillium chrysogenum DNA fragments cloned in EMBL3 or cosmid vectors from the upstream region of the pcbC-penDE cluster carry a gene (pcbAB) that complemented the deficiency ofExpand
Expression of the penDE gene of Penicillium chrysogenum encoding isopenicillin N acyltransferase in Cephalosporium acremonium: production of benzylpenicillin by the transformants
Analysis of the hybridization patterns of the DNA of C. acremonium transformed with the pcbC or penDE genes indicated that integration occurs by non-homologous recombination. Expand
Clusters of genes for the biosynthesis of antibiotics: Regulatory genes and overproduction of pharmaceuticals
  • J. Martín
  • Biology, Medicine
  • Journal of Industrial Microbiology
  • 2005
SummaryIn the last decade numerous genes involved in the biosynthesis of antibiotics, pigments, herbicides and other secondary metabolites have been cloned. The genes involved in the biosynthesis ofExpand
Characterization of a loss-of-function mutation in the isopenicillin N synthetase gene of Acremonium chrysogenum.
It is suggested that the N-2 strain of Acremonium chrysogenum carries a simple IPNS mutation and that IPNS or its biosynthetic product isopenicillin N is involved in regulation of the later stages of the Ce biosynthesis pathway. Expand
Characterization and expression in Streptomyces lividans of cefD and cefE genes from Nocardia lactamdurans: the organization of the cephamycin gene cluster differs from that in Streptomyces clavuligerus
expression of both genes, cefD and cefE, in S. lividans transformants, results in deacetoxycephalosporin C synthase and isopenicillin N epimerase activities that are 10–12 times higher than those in N. lactamdurans and S. clavuligerus. Expand