ArticleBMC systems biology2011
Degeneration of penicillin production in ethanol-limited chemostat cultivations of Penicillium chrysogenum: A systems biology approach.
Article in BMC systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Accumulation of the spontaneous and random mutations is causative of fungal culture degeneration.Fundamental research · 2026Article
- The Impact of DNA Methylation inMicroorganisms · 2025Article
- Adaptive Changes and Genetic Mechanisms in Organisms Under Controlled Conditions: A Review.International journal of molecular sciences · 2025Review
- High-throughput screening carbon and nitrogen sources to promote growth and sporulation in Rhizopus arrhizus.AMB Express · 2024Article
- The phenomenon of strain degeneration in biotechnologically relevant fungi.Applied microbiology and biotechnology · 2023Review
- Influence of oxygen concentration on the metabolism ofEngineering in life sciences · 2023Article
- Omics Approaches Applied toGenes · 2020Review
- Anticancer activity and metabolite profiling data ofData in brief · 2020Article
- Single-Cell Technologies to Understand the Mechanisms of Cellular Adaptation in Chemostats.Frontiers in bioengineering and biotechnology · 2020Article
- Functional characterization of a Penicillium chrysogenum mutanase gene induced upon co-cultivation with Bacillus subtilis.BMC microbiology · 2014Article
- Isolation of a Variant Strain of Pleurotus eryngii and the Development of Specific DNA Markers to Identify the Variant Strain.Mycobiology · 2014Article
- Linkage of oxidative stress and mitochondrial dysfunctions to spontaneous culture degeneration in Aspergillus nidulans.Molecular & cellular proteomics : MCP · 2014Article
- Systematic applications of metabolomics in metabolic engineering.Metabolites · 2012Article
- Impact of velvet complex on transcriptome and penicillin G production in glucose-limited chemostat cultures of a β-lactam high-producing Penicillium chrysogenum strain.Omics : a journal of integrative biology · 2012Article
- Resolving phenylalanine metabolism sheds light on natural synthesis of penicillin G in Penicillium chrysogenum.Eukaryotic cell · 2012Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn microbial production of non-catabolic products such as antibiotics a loss of production capacity upon long-term cultivation (for example chemostat), a phenomenon called strain degeneration, is often observed. In this study a systems biology approach, monitoring changes from gene to produced flux, was used to study degeneration of penicillin production in a high producing Penicillium chrysogenum strain during prolonged ethanol-limited chemostat cultivations.
resultsDuring these cultivations, the biomass specific penicillin production rate decreased more than 10-fold in less than 22 generations. No evidence was obtained for a decrease of the copy number of the penicillin gene cluster, nor a significant down regulation of the expression of the penicillin biosynthesis genes. However, a strong down regulation of the biosynthesis pathway of cysteine, one of the precursors of penicillin, was observed. Furthermore the protein levels of the penicillin pathway enzymes L-α-(δ-aminoadipyl)-L-α-cystenyl-D-α-valine synthetase (ACVS) and isopenicillin-N synthase (IPNS), decreased significantly. Re-cultivation of fully degenerated cells in unlimited batch culture and subsequent C-limited chemostats did only result in a slight recovery of penicillin production.
conclusionsOur findings indicate that the observed degeneration is attributed to a significant decrease of the levels of the first two enzymes of the penicillin biosynthesis pathway, ACVS and IPNS. This decrease is not caused by genetic instability of the penicillin amplicon, neither by down regulation of the penicillin biosynthesis pathway. Furthermore no indications were obtained for degradation of these enzymes as a result of autophagy. Possible causes for the decreased enzyme levels could be a decrease of the translation efficiency of ACVS and IPNS during degeneration, or the presence of a culture variant impaired in the biosynthesis of functional proteins of these enzymes, which outcompeted the high producing part of the population.
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