Aspergillus fumigatus is a human pathogen which causes serious disease in immunosuppressed, immunocompromised, and COVID-19 patients. It is a global concern for health and research is required to discover and optimise new management and treatment options for A. fumigatus infections. Essential metal homeostasis is a promising area of interest in managing fungal infection and exploiting natural products may generate new antifungal treatments. Secondary metabolite gliotoxin production and toxicity in A. fumigatus is intrinsically linked to zinc availability. The gene deletion mutant ΔgliTΔgtmA which lacks both the self-protective GliT and negative regulator of biosynthesis GtmA is hypersensitive to exogenous gliotoxin. This growth inhibition is overcome by zinc addition. Gliotoxin biosynthesis is abrogated by zinc availability, and partially restored by exogenous gliotoxin exposure. Deletion of gtmA results in altered zinc sensing in A. fumigatus, as seen by continued gliotoxin production in zinc replete conditions and altered proteomic response. The zinc-finger transcription factor GliZ is required for gli cluster activation and gliotoxin biosynthesis. Transient expression of GliZ fusion proteins under the endogenous promoter was overcome using a TET-On induction system. Doxycycline induction of tagged GliZ results in de novo gliotoxin biosynthesis and fusion protein detection in Sabouraud Dextrose media, which is non-permissive for gliotoxin biosynthesis. GliZ�HA abundance is increased in both gliotoxin and zinc presence, revealing an uncoupling of gli cluster transcription from zinc dependency. Oxidoreductase GliT is identified as a GliZ interacting protein uniquely after gliotoxin exposure. Plant derived natural product celastrol has many physiological effects. A. fumigatus is found to be susceptible to celastrol mediated growth inhibition. There is an altered response of A. fumigatus to celastrol depending on the availability of essential metals zinc and iron. In conclusion, the work presented in this thesis highlights the importance of metal�metabolite interactions in a pathogenic fungus and opens new avenues for investigation.