1. Field of the Invention
The present invention relates to methods for producing biological substances. The present invention also relates to isolated promoter variants and to nucleic acid constructs, vectors, and host cells comprising the promoter variants operably linked to nucleic acid sequences encoding biological substances.
2. Description of the Related Art
The recombinant production of a native or heterologous biological substance in a fungal host cell, particularly a filamentous fungal cell such as Aspergillus, may provide for a more desirable vehicle for producing the substance in commercially relevant quantities.
Recombinant production of a native or heterologous biological substance is accomplished by constructing an expression cassette in which the DNA coding for the protein is placed under the expression control of a promoter, excised from a regulated gene, suitable for the host cell. The expression cassette is introduced into the host cell, usually by plasmid-mediated transformation. Production of the substance is then achieved by culturing the transformed host cell under inducing conditions necessary for the proper functioning of the promoter contained on the expression cassette.
The development of a new fungal host cell for the recombinant production of biological substances generally requires the availability of promoters that are suitable for controlling the expression of the substances in the host cell. Fusarium venenatum has been shown to be useful as a new host cell for such expression (WO 96/00787, WO 97/26330). Moreover, the promoter from the Fusarium oxysporum trypsin-like protease gene has been described which is useful for expressing heterologous genes in Fusarium venenatum host cells (U.S. Pat. No. 5,837,847). U.S. Pat. No. 6,361,973 discloses a glucoamylase promoter from Fusarium venenatum. However, there is a need in the art for new promoters for controlling the expression of native and heterologous genes.
It is an object of the present invention to provide improved methods for producing a biological substance in a fungal host cell and new promoter variants for such production.