Project Details
Description
Hidden Drugs from Mould
Fungi present a rich source of secondary metabolites (SM) that are used in the battle of survival in their natural habitats and as infection facilitators during host pathogenesis. Each combatant has a specific arsenal that is characterized by inhibiting the growth of competing organisms. Well-known compounds derived from fungi are penicillin, cyclosporine A and lovastatin, which are all
blockbusters in the pharmaceutical industry. Fungal genome mining has revealed a wealth of unexplored gene candidates for synthesis of novel
SMs. Secondary metabolites from fungi are mainly produced by multidomain enzymes such as polyketide synthases or by nonribosomal peptide synthases. The synthesis of SMs are tightly regulated and only compounds that are produced in high amounts under standard culture conditions or during host infection have typically been characterized. The future challenge is to uncover the potential wealth of bioactive SMs for exploitation by the pharmaceutical industry and to address food safety aspects. Development of mechanisms that unleash the production of these secondary metabolites is required to explore the pharmaceutical potential of these fungi. The use of bioinformatics, over-expression of SM genes, histone modifications, challenging micro
organisms and diverse nutrient conditions has successfully resulted in the identification of aspoquinolone A and B, aspyridones A, asperfuranone from Aspergillus and cladochromes from Cladosporium 1. Thus, the time is ripe to unleash the wealth of SMs in an important plant pathogenic fungus such as Fusarium graminearum.
Aim:
Deliver pharmaceutical candidates by modification of the regulatory pathways of secondary
metabolites in Fusarium graminearum.
I will:
• Generate deletion and over-expression mutants to identify the products of silent SM genes
• Generate NRPS proteins that are tagged with flourochromes to track expression in vivo
• Identify regulation pathways of NRPSs by deepSAGE and iTRAQ to elevate the expression level
• Isolate and identify SM produced by NRPSs
• Test SM for bioactivity in both bacterial and mammalian cell cultures
• Carry out structural characterization of purified compounds
Fungi present a rich source of secondary metabolites (SM) that are used in the battle of survival in their natural habitats and as infection facilitators during host pathogenesis. Each combatant has a specific arsenal that is characterized by inhibiting the growth of competing organisms. Well-known compounds derived from fungi are penicillin, cyclosporine A and lovastatin, which are all
blockbusters in the pharmaceutical industry. Fungal genome mining has revealed a wealth of unexplored gene candidates for synthesis of novel
SMs. Secondary metabolites from fungi are mainly produced by multidomain enzymes such as polyketide synthases or by nonribosomal peptide synthases. The synthesis of SMs are tightly regulated and only compounds that are produced in high amounts under standard culture conditions or during host infection have typically been characterized. The future challenge is to uncover the potential wealth of bioactive SMs for exploitation by the pharmaceutical industry and to address food safety aspects. Development of mechanisms that unleash the production of these secondary metabolites is required to explore the pharmaceutical potential of these fungi. The use of bioinformatics, over-expression of SM genes, histone modifications, challenging micro
organisms and diverse nutrient conditions has successfully resulted in the identification of aspoquinolone A and B, aspyridones A, asperfuranone from Aspergillus and cladochromes from Cladosporium 1. Thus, the time is ripe to unleash the wealth of SMs in an important plant pathogenic fungus such as Fusarium graminearum.
Aim:
Deliver pharmaceutical candidates by modification of the regulatory pathways of secondary
metabolites in Fusarium graminearum.
I will:
• Generate deletion and over-expression mutants to identify the products of silent SM genes
• Generate NRPS proteins that are tagged with flourochromes to track expression in vivo
• Identify regulation pathways of NRPSs by deepSAGE and iTRAQ to elevate the expression level
• Isolate and identify SM produced by NRPSs
• Test SM for bioactivity in both bacterial and mammalian cell cultures
• Carry out structural characterization of purified compounds
| Status | Finished |
|---|---|
| Effective start/end date | 01/07/2011 → 30/06/2014 |
Funding
- FTP, Individuel post doc