Metabolic Constraints and Dependencies Between “Uncultivable” Fungi and Their Hosts

Many host-associated fungi are believed to be uncultivable because they have thus far never been brought into culture. However, the absence of success in bringing a fungus into cultivation in the laboratory should not be interpreted as an indication that the fungus cannot grow axenically without a living host. In this chapter, we review the history of the cultivation of fungi and provide examples where seemingly fastidious fungi have been successfully cultivated, borrowing insights from the literature on bacteria. We define a few of the hypotheses for why fungi become uncultivable and suggest that only organisms with a highly predictable environment will likely lose the ability to produce primary metabolites needed for making cells. Highly host-specific parasites fit this description, while arbuscular mycorrhizae do not. As fungal genomics has blossomed, it provides an unprecedented opportunity to investigate, from a genetic-biochemistry level, particular metabolic requirements that may provide insights into cultivation strategies. Common themes across diverse fungi are the loss of pathways for synthesis of long-chain fatty acids, amino acids, and vitamins. Finally, we discuss novel approaches and experimental systems that may be used to overcome the common barriers to cultivation.