Proteomic analysis of Acremonium chrysogenum WT (ATCC 11550) and HY (RNCM F-4081D) strains

Description

Acremonium chrysogenum is the only industrial producer of the antibiotic cephalosporin C (CPC), the starting substance for manufacturing of cephalosporins of the 1st-5th generation. Producing strains used in industry are significantly improved through multiple rounds of random mutagenesis; however, the molecular basis for such changes is not fully understood. In this study, we attempt to elucidate key changes that occurred at proteome level in the CSI program of A. chrysogenum HY (RNCM F-4081D), with CPC production 300-fold higher than in parental A. chrysogenum WT strain (ATCC 11550). It was revealed that more than 30% of proteins are differentially expressed at different stages of fermentation. Among identified changes, the most critical appears to be upreg-ulation of beta-lactam biosynthetic enzymes. The data also suggest shifts in the primary metabolic pathways, providing building blocks for beta-lactam synthesis reactions, in-cluding the amino acid precursors cysteine, valine, and substrate for expandase reaction, α-ketoglutarate. Changes in energy flows in favor of targeted metabolic pathway were also revealed. High-yielding CPC production appears to be accompanied by oxidative stress, as key oxidative stress enzymes are upregulated. Our findings are consistent with previous investigations describing changes that occurred in other fungal strains improved by classical methods. This points to general key changes leading to high-yield production. A deeper understanding of these features is important for predicting the target effects of improved industrial producers of secondary metabolites. Here we provide data on the proteomic analysis performed: Table 1: Data after proteomic analysis by LC-MS/MS of samples isolated from A. chrysogenum HY and WT strains after 72, 96 and 120 h of fermentation; Table 2: emPAI of individual proteins within proteomes, normalized to GAPDH; Table 3: Hierarchical cluster analysis of DEPs in A. chrysogenum WT and HY strains; Table 4: Enrichment analysis of overrepresented GO terms in DEPs in A. chrysogenum strains (HY vs. WT); Table 5: Hierarchical cluster analysis of DEPs in A. chrysogenum WT during fermentation and in A. chrysogenum HY during fermentation; Table 6: Enrichment analysis of overrepresented GO terms in DEPs in A. chrysogenum WT (96/72 and 120/72 h) and in A. chrysogenum HY (96/72 and 120/72 h).

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Funders

• The Ministry of Education and Science of the Russian Federation

  Russia

  Grant ID: Project 125052006274-4

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