ABSTRACT

At the time of writing, high-quality draft genomic sequences of five ascomycete yeasts, Saccharomyces cerevisiae, S. paradoxus, S. bayanus, S. milkatae, and Schizosaccharomyces pombe, and the first filamentous fungus, Neurospora crassa, have been completed. Completion of the sequence of Saccharomyces cerevisiae, one of man’s oldest domesticated partners, was a landmark in molecular biology and has enabled scientists to globally study eukaryotic gene expression and gene function. Sequencing projects for at least another dozen species of fungi, representing both the phylogenetic breadth of fungi and some of the most medically and economically significant species are in progress or in the planning stages [1]. The sequences of these fungi reveal organisms that are remarkably similar in genomic complexity, organization, and function to other eukaryotes. For example, N. crassa is estimated to have around 10,000 genes, roughly 70% as many as Drosophilia melanogaster (14,000 genes), 50% as many as Caenorhabditis elegans (20,000 genes), and about 30% as many as Homo sapiens (21,000-39,000 genes). About 4000 of the estimated proteins ofN. crassa are without obvious counterparts in public databases, which

may be a function of general lack of fungal genomic data and points to the enormous potential for new gene discovery in fungi. Among the 1400 genes that have counterparts with other eukaryotes are genes associated with a biological clock, light sensing, and many core signaling pathways for cellular functioning. Surprisingly, more than half the genes of N. crassa have no counterpart in S. cerevisiae or Sch. pombe, hinting at the potential genetic diversity in fungi, considering these are only three species among the estimated 150,000 species of ascomycetes [2]. Genomic analyses of Neurospora crassa have identified some seven polyketide synthases gene clusters, three nonribosomal peptide synthases, and several genes associated with diterpene biosynthesis. The complete or partial gene clusters of secondary metabolite biosynthetic pathways have now been characterized for only several dozen fungi. The finding of such extensive biosynthetic capacity in a fungus that is generally thought to be devoid of secondary metabolites, except for carotenoids and melanin pigments, reveals that our knowledge of secondary metabolites of fungi and how to elaborate and engineer their production is still in its infancy.