Pathways and Enzymes from Fungal Genomes for Degradation of Aromatic Compounds

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In recent years there has been considerable interest in many countries, especially the US, in sequencing the genomes of fungi. Sequencing a genome nowadays is relatively easy and inexpensive, and there are over 150 fungal genome sequences available in public databases, with the number growing fast. Fungi are the master degraders and recyclers of the biosphere, and have the ability to transform almost any material, first into its constituent parts and then carbon dioxide and water. They do so in order to obtain carbon and energy to grow, using protein catalysts called enzymes to drive each step in the degradation process. Much of the interest in sequencing fungal genomes lies in the possibility of identifying genes encoding the complete repertoire of enzymes that each fungus has to contribute to these degradation activities. Once identified, it is believed that the degradative power of these enzymes can be harnessed to degrade complex plant materials to useful products, such as ethanol and fine chemicals, or to destroy pollutants. Indeed, many commercial processes, from baking to biofuel production already rely on fungal enzymes. However these come from a handful of fungi, and with well over a million fungal species in the world living in a wide variety of habitats, there is a huge reservoir of potentially useful enzymes that remains untapped. One group of chemicals that fungi can degrade are the aromatic compounds, which are defined by the presence of one or more benzene rings, but otherwise are very diverse in terms of what is attached to those rings. A large variety of aromatic compounds is made by plants, and we are exposed to those in our diets, but we also use large quantities of aromatics for manufacturing and in industrial processes. Although human metabolism of such compounds is generally directed towards detoxification and elimination, fungi and bacteria utilize them as sole sources of carbon and energy to grow. While many genes in fungal genomes have been assigned functions in the degradation of aromatic compounds, there is often very little experimental evidence that supports these assignments. The aim of this proposal is to connect fungal genome sequence data to experimental evidence for the functions of genes and their encoded enzymes in metabolic pathways used for the degradation of aromatic compounds. Initially, we are focusing on a few species, with known abilities to degrade a range of these compounds, to produce well-defined and complete sets of data for the genes and corresponding enzymes involved in the degradation pathways. From these well-defined examples we will expand to other species across the fungal tree of life, and to a broader range of compounds. This work is expected to be significant in a number of ways. First, it will allow a large group of genes in fungal genomes, which currently are poorly or incorrectly understood, to be solidly linked to functional properties. Many experimental studies that use the genome information can only be interpreted properly with the information that we will be generating. Second, it will reveal strategies, currently not well understood, used by fungi for the degradation of a large group of compounds of environmental significance and potentially related to human health. This will allow better prediction of the fate of aromatic compounds in the environment and the metabolic capabilities of fungi. Third, it is anticipated that some of the enzymes identified will have novel catalytic properties that will contribute to new biochemical knowledge and be useful for specific applications as catalysts, for example in the degradation of chemical wastes or conversion or plant waste to biodiesel.