title: Establishing a synthetic pathway for high-level production of 3-hydroxypropionic acid in Saccharomyces cerevisiae via β-alanine.
abstract: Microbial fermentation of renewable feedstocks into plastic monomers can decrease our fossil dependence and reduce global CO2 emissions. 3-Hydroxypropionic acid (3HP) is a potential chemical building block for sustainable production of superabsorbent polymers and acrylic plastics. With the objective of developing Saccharomyces cerevisiae as an efficient cell factory for high-level production of 3HP, we identified the β-alanine biosynthetic route as the most economically attractive according to the metabolic modeling. We engineered and optimized a synthetic pathway for de novo biosynthesis of β-alanine and its subsequent conversion into 3HP using a novel β-alanine-pyruvate aminotransferase discovered in Bacillus cereus. The final strain produced 3HP at a titer of 13.7±0.3gL(-1) with a 0.14±0.0C-molC-mol(-1) yield on glucose in 80h in controlled fed-batch fermentation in mineral medium at pH 5, and this work therefore lays the basis for developing a process for biological 3HP production.
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark. Electronic address: irbo@biosustain.dtu.dk.
authors.forename: Irina
authors.initials: I
authors.lastname: Borodina
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Kanchana R
authors.initials: KR
authors.lastname: Kildegaard
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Niels B
authors.initials: NB
authors.lastname: Jensen
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3b, DK-2200 Copenhagen N, Denmark.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Blicher
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Maury
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Sherstyk
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Schneider
authors.affiliation: CERMAX-Centro de Ressonância Magnética António Xavier, ITQB-Instituto de Tecnologia Química e Biológica, Av. da República (EAN), Apartado 127, 2781-901 Oeiras, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Lamosa
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Herrgård
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Inger
authors.initials: I
authors.lastname: Rosenstand
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Öberg
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark.
authors.forename: Jochen
authors.initials: J
authors.lastname: Forster
authors.affiliation: The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle allé 6, DK-2970 Hørsholm, Denmark; Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-412 96 Göteborg, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D001409:Bacillus cereus / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis; D060847:Metabolic Engineering; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015091:beta-Alanine / Q000235:genetics / Q000378:metabolism; D051278:beta-Alanine-Pyruvate Transaminase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D015091:beta-Alanine; D019344:Lactic Acid; C031601:hydracrylic acid; D051278:beta-Alanine-Pyruvate Transaminase
keywords: 3-hydroxypropionic acid; Biosustainable acrylics; Saccharomyces cerevisiae; β-alanine; β-alanine-pyruvate aminotransferase