{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13"],"submitter":["Li J"],"pubmed_abstract":["This study engineered the thermotolerant yeast <i>Kluyveromyces marxianus</i> to produce 3-hydroxypropionic acid (3-HP), a key precursor for biodegradable plastics, via the malonyl-CoA pathway using non-food feedstocks. The 3-HP titer was further increased through deleting <i>Adh2A</i> and <i>Ach1</i>, which prevents the synthesis of byproducts ethanol and acetic acid. Using Jerusalem artichoke tuber powder, engineered strain produced 27.32 and 32.31 g/L of 3-HP at 37 °C and 42 °C through fed-batch fermentation. Metabolic reconstruction replaced the native FADH<sub>2</sub>-dependent glycerol pathway (GUT1/GUT2) with an NADH-generating GDH1/DAK1 pathway, significantly enhancing glycerol utilization and increasing intracellular NADH supply by 62 %. Overexpression of <i>Utr1</i> can further enhance the NADPH supply. Combined with heterologous expression of a codon-optimized, high-activity malonyl-CoA reductase (MCR) mutant (MCR<sup>N940V/K1106W/S1114R</sup>), the engineered strain achieved 3-HP titers of 33.15 g/L in fed-batch fermentation using pure glycerol at 42 °C. Crucially, it also produced 26.57 g/L 3-HP directly from crude glycerol at 42 °C. The thermotolerant fermentation at 42 °C, unprecedented for yeast-based 3-HP synthesis, reduces cooling water consumption by approximately 60 %, translating to an estimated annual CO<sub>2</sub> reduction of 27.1 tons per 1000-ton fermenter. This work establishes a cost-effective, industrially scalable bioprocess for valorizing Jerusalem artichoke tubers and crude glycerol into a key platform chemical for biodegradable plastics and green chemicals, leveraging the strain's substrate flexibility, process robustness, and significant environmental advantages."],"journal":["Synthetic and systems biotechnology"],"pagination":["1-13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12856427"],"repository":["biostudies-literature"],"pubmed_title":["Engineering &lt;i&gt;Kluyveromyces marxianus&lt;/i&gt; for 3-hydroxypropionic acid production at elevated temperature from Jerusalem artichoke tubers and crude glycerol."],"pmcid":["PMC12856427"],"pubmed_authors":["Li Y","Zhao M","Li J","Xie Y","Ren L","Hu Z","Zhang B","Zha H"],"additional_accession":[]},"is_claimable":false,"name":"Engineering &lt;i&gt;Kluyveromyces marxianus&lt;/i&gt; for 3-hydroxypropionic acid production at elevated temperature from Jerusalem artichoke tubers and crude glycerol.","description":"This study engineered the thermotolerant yeast <i>Kluyveromyces marxianus</i> to produce 3-hydroxypropionic acid (3-HP), a key precursor for biodegradable plastics, via the malonyl-CoA pathway using non-food feedstocks. The 3-HP titer was further increased through deleting <i>Adh2A</i> and <i>Ach1</i>, which prevents the synthesis of byproducts ethanol and acetic acid. Using Jerusalem artichoke tuber powder, engineered strain produced 27.32 and 32.31 g/L of 3-HP at 37 °C and 42 °C through fed-batch fermentation. Metabolic reconstruction replaced the native FADH<sub>2</sub>-dependent glycerol pathway (GUT1/GUT2) with an NADH-generating GDH1/DAK1 pathway, significantly enhancing glycerol utilization and increasing intracellular NADH supply by 62 %. Overexpression of <i>Utr1</i> can further enhance the NADPH supply. Combined with heterologous expression of a codon-optimized, high-activity malonyl-CoA reductase (MCR) mutant (MCR<sup>N940V/K1106W/S1114R</sup>), the engineered strain achieved 3-HP titers of 33.15 g/L in fed-batch fermentation using pure glycerol at 42 °C. Crucially, it also produced 26.57 g/L 3-HP directly from crude glycerol at 42 °C. The thermotolerant fermentation at 42 °C, unprecedented for yeast-based 3-HP synthesis, reduces cooling water consumption by approximately 60 %, translating to an estimated annual CO<sub>2</sub> reduction of 27.1 tons per 1000-ton fermenter. This work establishes a cost-effective, industrially scalable bioprocess for valorizing Jerusalem artichoke tubers and crude glycerol into a key platform chemical for biodegradable plastics and green chemicals, leveraging the strain's substrate flexibility, process robustness, and significant environmental advantages.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Sep","modification":"2026-06-18T05:50:21.13Z","creation":"2026-06-18T03:07:49.033Z"},"accession":"S-EPMC12856427","cross_references":{"pubmed":["41624984"],"doi":["10.1016/j.synbio.2026.01.008"]}}