# Accessible Type 2 diabetes medication through stable expression of Exendin-4 in Saccharomyces cerevisiae

**Authors:** Gia Balius, Kiana Imani, Zoë Petroff, Elizabeth Beer, Thiago Brasileiro Feitosa, Nathan Mccall, Lauren Paule, Neo Yixuan Peng, Joanne Shen, Vidhata Singh, Cambell Strand, Jonathan Zau, D. L. Bernick

PMC · DOI: 10.3389/fsysb.2024.1283371 · Frontiers in Systems Biology · 2024-09-02

## TL;DR

This paper explores using yeast to produce a diabetes drug called Exendin-4, aiming to make it more affordable and accessible.

## Contribution

The novel contribution is the successful expression of Exendin-4 in Saccharomyces cerevisiae, a safe and cost-effective organism.

## Key findings

- Exendin-4 was successfully expressed in S. cerevisiae at the expected size.
- The expressed protein was confirmed using immunoassay techniques.
- This yeast-based production could lead to affordable diabetes treatment.

## Abstract

Diabetes mellitus affects roughly one in ten people globally and is the world’s ninth leading cause of death. However, a significant portion of chronic complications that contribute to mortality can be prevented with proper treatment and medication. Glucagon-like peptide 1 receptor agonists, such as Exendin-4, are one of the leading classes of Type 2 diabetes treatments but are prohibitively expensive. In this study, experimental models for recombinant Exendin-4 protein production were designed in both Escherichia coli and Saccharomyces cerevisiae. Protein expression in the chromosomally integrated S. cerevisiae strain was observed at the expected size of Exendin-4 and confirmed by immunoassay. This provides a foundation for the use of this Generally Regarded as Safe organism as an affordable treatment for Type 2 diabetes that can be propagated, prepared, and distributed locally.

## Linked entities

- **Diseases:** Type 2 diabetes (MONDO:0005148)
- **Species:** Saccharomyces cerevisiae (taxon 4932), Escherichia coli (taxon 562)

## Full-text entities

- **Genes:** LEU2 (3-isopropylmalate dehydrogenase) [NCBI Gene 850342], INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, HSP12 (lipid-binding protein HSP12) [NCBI Gene 850532] {aka GLP1, HOR5}, GAL1 (galactokinase) [NCBI Gene 852308], TRP1 (phosphoribosylanthranilate isomerase TRP1) [NCBI Gene 851570], DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, PGK1 (phosphoglycerate kinase) [NCBI Gene 850370]
- **Diseases:** T2D (MESH:D003924), death (MESH:D003643), heart failure (MESH:D006333), neuropathy (MESH:D009422), insulin resistance (MESH:D007333), kidney disease (MESH:D007674), blindness (MESH:D001766), Diabetes mellitus (MESH:D003920)
- **Chemicals:** SDS (MESH:D012967), amino acid (MESH:D000596), tryptophan (MESH:D014364), VPGVG (MESH:C094883), maltose (MESH:D008320), agar (MESH:D000362), lactose (MESH:D007785), Agarose (MESH:D012685), NaCl (MESH:D012965), G418 sulfate (MESH:C010680), KCl (MESH:D011189), ATP (MESH:D000255), glycerol (MESH:D005990), leucine (MESH:D007930), sugars (MESH:D000073893), Kanamycin (MESH:D007612), potassium phosphate (MESH:C013216), hygromycin (MESH:C026273), IPTG (MESH:D007544), Triton X-100 (MESH:D017830), sucrose (MESH:D013395), glucose (MESH:D005947), 3.4 Galactose (-), blood glucose (MESH:D001786), water (MESH:D014867), Ex-4 (MESH:D000077270), His (MESH:D006639), cAMP (MESH:D000242), Imidazole (MESH:C029899)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Alternaria sp. DY (species) [taxon 1852173], Escherichia coli BL21(DE3) (strain) [taxon 469008], Homo sapiens (human, species) [taxon 9606], Heloderma suspectum (Gila monster, species) [taxon 8554]
- **Mutations:** N3200S, T1010S
- **Cell lines:** DH5alpha — Drosophila hydei (Fruit fly), Spontaneously immortalized cell line (CVCL_Z531), ex4 — Dascyllus trimaculatus (Tree-spot damselfish), Spontaneously immortalized cell line (CVCL_1G84), pET28 — Oryctolagus cuniculus (Rabbit), Transformed cell line (CVCL_6E94), BL21 (DE3) — Mus musculus (Mouse), Hybridoma (CVCL_B7HM)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12342014/full.md

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12342014/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12342014/full.md

---
Source: https://tomesphere.com/paper/PMC12342014