Compositions and methods related to fungal hypoxia responsive morphology factor a (hrmA) and biofilm architecture factor (baf) proteins

Patent metadata

Field	Value
Publication number	US-12116579-B2
Application number	US-202017642592-A
Country	US
Kind code	B2
Filing date	Sep 11, 2020
Priority date	Sep 12, 2019
Publication date	Oct 15, 2024
Grant date	Oct 15, 2024

Abstract

Filamentous fungal host cells expressing hypoxia responsive morphology factor A (hrmA) and biofilm architecture factor (baf) proteins are provided. Methods of producing filamentous fungal host cells expressing hrmA and baf proteins are also provided. In one aspect, the disclosure provides a filamentous fungal host cell, comprising a nucleotide sequence encoding an Aspergillus fumigatus hypoxia responsive morphology factor A (hrmA) protein, or a homolog or ortholog thereof.

First claim

What is claimed:

1. A filamentous fungal host cell, comprising an exogenous nucleotide sequence encoding an Aspergillus fumigatus biofilm architecture factor (baf) protein, wherein the baf protein comprises (a) bafA, or a homolog or ortholog thereof having bafA activity, (b) bafB, or a homolog or ortholog thereof having bafB activity, and (c) bafC, or a homolog or ortholog thereof having bafC activity, the bafA protein or a homolog or ortholog thereof having bafA activity comprising at least 90% identity to the amino acid sequence of SEQ ID NO: 13; the bafB protein or a homolog or ortholog thereof having bafB activity comprising at least 90% identity to the amino acid sequence of SEQ ID NO: 14; and the bafC protein or a homolog or ortholog thereof having bafC activity comprising at least 90% identity to the amino acid sequence of SEQ ID NO: 15.

2. The filamentous fungal host cell of claim 1 , wherein
the filamentous fungal host cell is not Aspergillus fumigatus.

3. The filamentous fungal host cell of claim 1 , wherein
the bafA protein comprises the amino acid sequence of SEQ ID NO: 13; or the bafB protein comprises the amino acid sequence of SEQ ID NO: 14; or the bafC protein comprises the amino acid sequence of SEQ ID NO: 15.

4. A method of increasing fungal secretion of one or more products of interest, increasing the production of one or more products of interest, and/or reducing oxygen consumption of a filamentous fungal host cell, the method comprising introducing into the filamentous fungal host cell one or more polynucleotide sequences encoding one or both of an hrmA protein and a baf protein to make the filamentous fungal host cell of claim 1 .

5. The method of claim 4 , wherein
the hrmA protein comprises the amino acid sequence of SEQ ID NO: 12; and/or the baf protein comprises the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16.

6. The method of claim 4 , wherein oxygen consumption is reduced by 10% to 90%.

7. The method of claim 4 , wherein the polynucleotide sequence is introduced into the filamentous fungal host cell via transformation, optionally wherein the transformation comprises one or more of protoplast-mediated transformation, Agrobacterium -mediated transformation, electroporation, biolistic transformation, and shock-wave-mediated transformation.

Assignees

• Dartmouth College

Inventors

• Cramer Jr Robert A
• Kowalski Caitlin

Classifications

• C12N15/52

  Genes encoding for enzymes or proenzymes · CPC title

• C07K14/38

  from Aspergillus · CPC title

• C12P17/06

  containing a six-membered hetero ring, e.g. fluorescein · CPC title

• C12P7/46

  Dicarboxylic acids having four or less carbon atoms, e.g. fumaric acid, maleic acid · CPC title

• C12P7/58

  Aldonic, ketoaldonic or saccharic acids (uronic acids C12P19/00) · CPC title