Transcriptome analysis of the two unrelated fungal \(\beta\)-lactam producers \(\textit {Acremonium chrysogenum}\) and \(\textit {Penicillium chrysogenum}\)

  • \(\textbf {Background:}\) Cephalosporins and penicillins are the most frequently used \(\beta\)-lactam antibiotics for the treatment of human infections worldwide. The main industrial producers of these antibiotics are \(\textit {Acremonium chrysogenum}\) and \(\textit {Penicillium chrysogenum}\), two taxonomically unrelated fungi. Both were subjects of long-term strain development programs to reach economically relevant antibiotic titers. It is so far unknown, whether equivalent changes in gene expression lead to elevated antibiotic titers in production strains. \(\textbf {Results:}\) Using the sequence of PcbC, a key enzyme of \(\beta\)-lactam antibiotic biosynthesis, from eighteen different pro- and eukaryotic microorganisms, we have constructed a phylogenetic tree to demonstrate the distant relationship of both fungal producers. To address the question whether both fungi have undergone similar genetic adaptions, we have performed a comparative gene expression analysis of wild-type and production strains. We found that strain improvement is associated with the remodeling of the transcriptional landscape in both fungi. In \(\textit {P. chrysogenum}\), 748 genes showed differential expression, while 1572 genes from \(\textit {A. chrysogenum}\) are differentially expressed in the industrial strain. Common in both fungi is the upregulation of genes belonging to primary and secondary metabolism, notably those involved in precursor supply for \(\beta\)-lactam production. Other genes not essential for \(\beta\)-lactam production are downregulated with a preference for those responsible for transport processes or biosynthesis of other secondary metabolites. Transcriptional regulation was shown to be an important parameter during strain improvement in different organisms. We therefore investigated deletion strains of the major transcriptional regulator \(\it velvet\) from both production strains. We identified 567 \(\textit {P. chrysogenum}\) and 412 \(\textit {A. chrysogenum}\) Velvet target genes. In both deletion strains, approximately 50% of all secondary metabolite cluster genes are differentially regulated, including \(\beta\)-lactam biosynthesis genes. Most importantly, 35-57% of Velvet target genes are among those that showed differential expression in both improved industrial strains. \(\textbf {Conclusions:}\) The major finding of our comparative transcriptome analysis is that strain improvement programs in two unrelated fungal \(\beta\)-lactam antibiotic producers alter the expression of target genes of Velvet, a global regulator of secondary metabolism. From these results, we conclude that regulatory alterations are crucial contributing factors for improved \(\beta\)-lactam antibiotic titers during strain improvement in both fungi.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Dominik TerfehrGND, Tim Alexander DahlmannORCiDGND, Ulrich KückORCiDGND
URN:urn:nbn:de:hbz:294-58955
DOI:https://doi.org/10.1186/s12864-017-3663-0
Parent Title (English):BMC genomics
Subtitle (English):velvet-regulated genes are major targets during conventional strain improvement programs
Document Type:Article
Language:English
Date of Publication (online):2018/07/10
Date of first Publication:2017/03/31
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
Acremonium chrysogenum; Amino acid metabolism; Cephalosporin; Gene expression; Penicillin; Penicillium chrysogenum; RNA- seq; Secondary metabolism; Strain improvement; Velvet
Volume:18
Issue:1
First Page:1
Last Page:19
Note:
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Lehrstuhl für Allgemeine und Molekulare Botanik
Dewey Decimal Classification:Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie
open_access (DINI-Set):open_access
faculties:Fakultät für Biologie und Biotechnologie
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International