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Comparative proteomics reveals the mechanism of cyclosporine production and mycelial growth in Tolypocladium inflatum affected by different carbon sources

Summary

Researchers studied how different sugars (fructose and sucrose) affect a fungus’s ability to produce cyclosporine A, an important drug used after organ transplants to prevent rejection. Using advanced protein analysis techniques, they found that fructose makes the fungus better at producing the drug, while sucrose makes it grow more mycelium (fungal threads). By identifying the specific proteins involved in each process, scientists can now develop better methods to produce more of this valuable medicine.

Background

Cyclosporine A (CsA) is an important secondary metabolite from the fungus Tolypocladium inflatum with widespread clinical use as an immunosuppressant. Carbon sources significantly influence both CsA production and mycelial growth, but the underlying mechanisms remain poorly understood. This study aims to elucidate how different carbon sources affect CsA biosynthesis and fungal growth through proteomics analysis.

Objective

To identify and characterize the proteins and metabolic pathways that regulate cyclosporine A production and mycelial growth in T. inflatum when cultured on different carbon sources (fructose vs. sucrose). The study aims to provide molecular insights for developing high-efficiency CsA fermentation and metabolic engineering strategies.

Results

Fructose medium promoted CsA production (73.38 μg/5 mL/day on day 6) while sucrose favored mycelial accumulation (10.58 mg DW/5 mL). Analysis revealed 244 DEPs, with 74 highly expressed in fructose medium related to small molecule metabolism, lipid metabolism, and CsA substrate Bmt synthesis. In sucrose medium, 170 DEPs were highly expressed, predominantly involved in carbohydrate metabolism, nucleotide metabolism, protein synthesis, cell wall integrity, and stress response pathways.

Conclusion

Different carbon sources create distinct metabolic priorities in T. inflatum, with fructose promoting secondary metabolism and CsA biosynthesis through enhanced acid and lipid metabolism, while sucrose supports primary metabolism and mycelial biomass accumulation. These findings provide valuable candidate proteins and genes for metabolic engineering approaches to enhance CsA production efficiency in industrial fermentation.
  • Published in:Frontiers in Microbiology,
  • Study Type:Comparative Proteomics Study,
  • Source: 10.3389/fmicb.2023.1259101; PMID: 38163081
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