ArticleBMC genomics2015
Genomic mutational analysis of the impact of the classical strain improvement program on β-lactam producing Penicillium chrysogenum.
Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 60 citations in OpenAlex.
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- Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-YieldingMolecules (Basel, Switzerland) · 2021Article
- Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens.Journal of industrial microbiology & biotechnology · 2021Review
- CRISPR-based transcriptional activation tool for silent genes in filamentous fungi.Scientific reports · 2021Article
- Identification of a conserved N-terminal domain in the first module of ACV synthetases.MicrobiologyOpen · 2021Article
- Comparative genomics of Alexander Fleming's original Penicillium isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes.Scientific reports · 2020Article
- Omics Approaches Applied toGenes · 2020Review
- Studying the Gene Expression ofAntibiotics (Basel, Switzerland) · 2020Article
- Insight into the Genome of DiverseInternational journal of molecular sciences · 2020Review
- A Penicillium rubens platform strain for secondary metabolite production.Scientific reports · 2020Article
- Impact of Classical Strain Improvement ofApplied and environmental microbiology · 2020Article
- The critical role of plasma membrane H+-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum.PloS one · 2020Article
- Synthetic control devices for gene regulation in Penicillium chrysogenum.Microbial cell factories · 2019Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPenicillium chrysogenum is a filamentous fungus that is employed as an industrial producer of β-lactams. The high β-lactam titers of current strains is the result of a classical strain improvement program (CSI) starting with a wild-type like strain more than six decades ago. This involved extensive mutagenesis and strain selection for improved β-lactam titers and growth characteristics. However, the impact of the CSI on the secondary metabolism in general remains unknown.
resultsTo examine the impact of CSI on secondary metabolism, a comparative genomic analysis of β-lactam producing strains was carried out by genome sequencing of three P. chrysogenum strains that are part of a lineage of the CSI, i.e., strains NRRL1951, Wisconsin 54-1255, DS17690, and the derived penicillin biosynthesis cluster free strain DS68530. CSI has resulted in a wide spread of mutations, that statistically did not result in an over- or underrepresentation of specific gene classes. However, in this set of mutations, 8 out of 31 secondary metabolite genes (20 polyketide synthases and 11 non-ribosomal peptide synthetases) were targeted with a corresponding and progressive loss in the production of a range of secondary metabolites unrelated to β-lactam production. Additionally, key Velvet complex proteins (LeaA and VelA) involved in global regulation of secondary metabolism have been repeatedly targeted for mutagenesis during CSI. Using comparative metabolic profiling, the polyketide synthetase gene cluster was identified that is responsible for sorbicillinoid biosynthesis, a group of yellow-colored metabolites that are abundantly produced by early production strains of P. chrysogenum.
conclusionsThe classical industrial strain improvement of P. chrysogenum has had a broad mutagenic impact on metabolism and has resulted in silencing of specific secondary metabolite genes with the concomitant diversion of metabolism towards the production of β-lactams.
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