Methods for improving malic acid production in filamentous fungi

摘要

The present invention relates to methods of producing a C4 dicarboxylic acid, comprising: (a) cultivating a filamentous fungal host cell comprising a polynucleotide selected from the group consisting of a heterologous first polynucleotide encoding a C4 dicarboxylic acid transporter, a heterologous second polynucleotide encoding a malate dehydrogenase, and a heterologous third polynucleotide encoding a pyruvate carboxylase; wherein the filamentous fungal host cell is capable of secreting increased levels of the C4 dicarboxylic acid compared to the filamentous fungal host cell without the heterologous polynucleotide when cultivated under the same conditions; and (b) recovering the C4 dicarboxylic acid. The present invention also relates to methods for increasing C4 dicarboxylic acid production, filamentous fungal host cells and malate dehydrogenase variants.

主权项

1. A filamentous fungal host cell comprising a heterologous polynucleotide encoding a malic acid transporter, wherein the malic acid transporter is selected from the group consisting of:
(a) a malic acid transporter comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 34; (b) a malic acid transporter encoded by a polynucleotide that hybridizes under very high stringency conditions with the full-length complementary strand to SEQ ID NO: 33; and (c) a malic acid transporter encoded by a polynucleotide comprising a nucleotide sequence having at least 95% sequence identity with SEQ ID NO: 33; and wherein the filamentous fungal host cell is capable of secreting increased levels of malic acid compared to the filamentous fungal host cell without the heterologous polynucleotide encoding the malic acid transporter when cultivated under the same conditions.