Evidence map›Paper›PMID 31654411›Full record

ArticleBiotechnology and bioengineering2020

Comparative genome-scale analysis of Pichia pastoris variants informs selection of an optimal base strain.

Joseph R Brady, Charles A Whittaker, Melody C Tan, D Lee Kristensen, Duanduan Ma, Neil C Dalvie, Kerry Routenberg Love, J Christopher Love

Abstract read
In one paragraph

Article in Biotechnology and bioengineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

  1. Systematic optimization ofEngineering microbiology · 2026
    Review
  2. Article
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  4. Pichia-CLM: A language model-based codon optimization pipeline forProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
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  16. Safety of soy leghemoglobin from genetically modifiedEFSA journal. European Food Safety Authority · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. 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

8 authors.

Joseph R BradyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-2284-3872
Charles A WhittakerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Melody C TanKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
D Lee KristensenKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Duanduan MaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Neil C DalvieKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Kerry Routenberg LoveKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
J Christopher LoveKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Interdepartmental Biotechnology Training ProgramT32GM008334 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 1989 to 2018
$15.2M
AltHost ConsortiumBill and Melinda Gates Foundation OPP1154682NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NIGMS NIH HHS 2T32GM008334-26NIGMS NIH HHS T32 GM008334Space and Naval Warfare Systems Command N66001-13-C-4025
6 · The paper itself

Abstract

Komagataella phaffii, also known as Pichia pastoris, is a common host for the production of biologics and enzymes, due to fast growth, high productivity, and advancements in host engineering. Several K. phaffii variants are commonly used as interchangeable base strains, which confounds efforts to improve this host. In this study, genomic and transcriptomic analyses of Y-11430 (CBS7435), GS115, X-33, and eight other variants enabled a comparative assessment of the relative fitness of these hosts for recombinant protein expression. Cell wall integrity explained the majority of the variation among strains, impacting transformation efficiency, growth, methanol metabolism, and secretion of heterologous proteins. Y-11430 exhibited the highest activity of genes involved in methanol utilization, up to two-fold higher transcription of heterologous genes, and robust growth. With a more permeable cell wall, X-33 displayed a six-fold higher transformation efficiency and up to 1.2-fold higher titers than Y-11430. X-33 also shared nearly all mutations, and a defective variant of HIS4, with GS115, precluding robust growth. Transferring two beneficial mutations identified in X-33 into Y-11430 resulted in an optimized base strain that provided up to four-fold higher transformation efficiency and three-fold higher protein titers, while retaining robust growth. The approach employed here to assess unique banked variants in a species and then transfer key beneficial variants into a base strain should also facilitate rational assessment of a broad set of other recombinant hosts.

Indexed as

Fungal ProteinsGene Expression ProfilingGenome, FungalGenomicsPichiaRecombinant ProteinsRNA, FungalSaccharomycetalesSequence Analysis, RNATranscriptomeFungal ProteinsRecombinant ProteinsRNA, Fungalheterologous gene expressionrecombinant proteinRNA-Seqyeast

Identifiers

PMID31654411
PMCPMC7003935

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Registered trials

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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 OpenQuestion graph.