Evidence map›Paper›PMID 41513641›Full record

ArticleNature communications2026

High yield production of 3-hydroxypropionic acid using Issatchenkia orientalis.

Shih-I Tan, Sarang S Bhagwat, Teresa A Martin, Patrick F Suthers, Vinh G Tran, Wuying Tang, Zia Fatma, Costas D Maranas, Jeremy S Guest, Huimin Zhao

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Shih-I Tan *Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-7632-9991
Sarang S Bhagwat *Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-2620-2829
Teresa A Martin *Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Patrick F SuthersDOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-5560-9986
Vinh G TranDepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Wuying TangDepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Zia FatmaDepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Costas D MaranasDOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-1508-1398
Jeremy S GuestDOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, IL, USA. jsguest@illinois.edu.ORCID http://orcid.org/0000-0003-2489-2579
Huimin ZhaoDepartment of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA. zhao5@illinois.edu.ORCID http://orcid.org/0000-0002-9069-6739

Funding

U.S. Department of Energy (DOE) DE-SC0018420
6 · The paper itself

Abstract

Biomanufacturing provides a more sustainable alternative to fossil-based chemical manufacturing. 3-Hydroxypropionic acid (3HP) is a top Department of Energy value-added chemical and precursor to bioplastics, yet cost-effective microbial production remains elusive. Here, we establish the acid-tolerant yeast Issatchenkia orientalis as a robust host for low-pH 3HP biosynthesis. Genome-scale modeling identifies the β-alanine pathway as optimal, offering the highest theoretical yield and lowest oxygen requirement. Thermodynamic analysis confirms its favorability under acidic conditions. Using sequence similarity network analysis, we discover highly active aspartate 1-decarboxylase (PAND), β-alanine-pyruvate aminotransferase (BAPAT), and 3HP dehydrogenase (YDFG), which significantly improve the pathway efficiency. Next, to further elevate the production, pathway optimization through multi-copy PAND integration, byproduct elimination (knockouts of pyruvate decarboxylase and glycerol-3-phosphate dehydrogenase), and reinforcement of aspartate flux by overexpression of pyruvate carboxylase and aspartate amino transferase improves the titer to 29 g/L in shake flasks. Fed-batch fermentation at pH 4 with low-cost corn steep liquor medium further increases the production to 92 g/L with 0.7 g/g yield and 0.55 g/L/h productivity. Techno-economic analysis indicates that such performance could potentially enable a financially viable process for sustainable acrylic acid production. This work establishes I. orientalis as a next-generation platform for cost-effective 3HP production and paves the way toward industrial commercialization.

Indexed as

Lactic AcidSaccharomycetalesbeta-AlanineFermentationHydrogen-Ion ConcentrationMetabolic EngineeringPyruvate Decarboxylasebeta-Alaninehydracrylic acidLactic AcidPyruvate Decarboxylase

Identifiers

PMID41513641
PMCPMC12830792

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.