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Among the diversity of cellular systems that have been developed for the expression of heterologous gene products, certain species of filamentous fungi possess features which make them exceptionally attractive for this purpose. These include (a) the ability to produce high levels (>25 grams per liter) of secreted protein in submerged culture, (b) a long history of safe use in the production of enzymes, antibiotics, and biochemicals which are used for human consumption, and (c) established fermentation processes which are inexpensive by comparison with animal cell culture processes done on a similar scale. These attributes have prompted several biotechnology companies to explore the use of filamentous fungi as hosts for the expression and secretion of foreign proteins. Some of the heterologous gene products which have been made using fungal expression systems are shown in Table 1. Compared to highly refined expression systems such as Escherichia coli or Saccharomyces cerevisiae, the evolution of filamentous fungi as hosts has barely begun, and many fundamental aspects of cell biology and biochemistry in fungi have not been studied. Fortunately, many of the molecular details and principles which have been elucidated in yeast and in mammalian cell systems appear to be applicable to the study of heterologous gene expression and protein secretion in filamentous fungi as well.

Bacteriophage PBS1 and its clear-plaque variant PBS2 are unique viruses in that their DNA contains uracil instead of thymine (1,2). One of the changes affecting deoxyribonucleotide metabolism in Bacillus subtilis following PBS1 or PBS2 infection (see Fig. 1) is an increase in the level of DNA polymerase activity. We predicted that the phage-induced DNA polymerase would be a new enzyme, whose substrate in vivo would be dUTP for the synthesis of uracil-DNA. This report describes the discovery of dUTP in vivo, evidence for its biosynthetic origin, and characteristics of the purified phage DNA polymerase.