Evidence map›Paper›PMID 40367179›Full record

ArticleScience advances2025

Ancestral reconstruction of polyethylene terephthalate degrading cutinases reveals a rugged and unexplored sequence-fitness landscape.

Vanessa Vongsouthi, Rosemary Georgelin, Dana S Matthews, Jake Saunders, Brendon M Lee, Jennifer Ton, Adam M Damry, Rebecca L Frkic, Matthew A Spence, Colin J Jackson

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Disordered N-termini enhance the thermostability of SGNH-hydrolase family polyesterases.Protein science : a publication of the Protein Society · 2026
    Article
  6. Article
  7. Article
  8. Review
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.

Vanessa VongsouthiResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0001-9645-0003
Rosemary GeorgelinResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0002-1841-1479
Dana S MatthewsResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0009-0009-7283-4884
Jake SaundersResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0001-9290-2287
Brendon M LeeResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Jennifer TonSamsara Eco, Sydney, NSW 2065, Australia.
Adam M DamryResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0003-3596-3133
Rebecca L FrkicResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Matthew A SpenceResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0003-2284-2498
Colin J JacksonResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0001-6150-3822

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of protein engineering to generate enzymes for the degradation of polyethylene terephthalate (PET) is a promising route for plastic recycling, yet traditional engineering approaches often fail to explore protein sequence space for optimal enzymes. In this work, we use multiplexed ancestral sequence reconstruction (mASR) to address this, exploring the evolutionary sequence space of PET-degrading cutinases. Using 20 statistically equivalent phylogenies of the bacterial cutinase family, we generated 48 ancestral sequences revealing a wide range of PETase activities, highlighting the value of mASR in uncovering functional variants. Our findings show PETase activity can evolve through multiple pathways involving mutations remote from the active site. Moreover, analyzing the PETase fitness landscape with local ancestral sequence embedding (LASE) revealed that LASE can capture sequence features linked to PETase activity. This work highlights mASR's potential in exploration of sequence space and underscores the use of LASE in readily mapping the protein fitness landscapes.

Indexed as

Bacterial ProteinsCarboxylic Ester HydrolasesPolyethylene TerephthalatesEvolution, MolecularMutationPhylogenyProtein EngineeringBacterial ProteinsCarboxylic Ester HydrolasescutinasePolyethylene Terephthalates

Identifiers

PMID40367179
PMCPMC12077509

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.