Technical University of Denmark

Jochen Förster

Irina Borodina

Kanchana Rueksomtawin Kildegaard

Jens Nielsen

Niels Bjerg Jensen

Yun Chen

Jerome Maury

Fredrik Öberg

Cells and cell cultures are provided that have improved tolerance to 3-hydroxypropionic acid (3HP). Genetic modifications to provide a mutated or overexpressed SFA1 gene or other enhancement of 3HP detoxification via a glutathione-dependent dehydrogenase reaction, including medium supplementation with glutathione, may be combined with a 3HP producing metabolic pathway.

3HP tolerance

A yeast cell having a reduced level of activity of NAD dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has at least one exogenous gene encoding NADP dependent GAPDH and/or has up-regulation of at least one endogenous gene expressing NADP dependent GAPDH, wherein combined expression of the enzymes NADP dependent GAPDH, PDC, ALD, ACS, ACC* and MCR in said host cell increases metabolic flux towards 3-HP via malonyl-CoA compared to an otherwise similar yeast cell lacking said genetic modification.

Microbial production of 3-hydroxypropionic acid

A genetically modifiedincluding an active fermentation pathway producing 3-HP expresses an exogenous gene expressing the aminotransferase YhxA fromAH1272 catalyzing a transamination reaction between beta-alanine and pyruvate to produce malonate semialdehyde. The yeast may also express a 3-hydroxyisobutyrate dehydrogenase (HIBADH) and a 3-hydroxypropanoate dehydrogenase (3-HPDH) and aspartate 1-decarboxylase. Additionally the yeast may express pyruvate carboxylase and aspartate aminotransferase.

Genetically engineered yeast

Growing community of inventors

Kgs. Lyngby, Denmark

Jochen Förster