Evidence map›Paper›PMID 33738790›Full record

ArticleBiotechnology and bioengineering2021

Lactoyl leucine and isoleucine are bioavailable alternatives for canonical amino acids in cell culture media.

Corinna Schmidt, Maria Wehsling, Maxime Le Mignon, Gregor Wille, Yannick Rey, Alisa Schnellbaecher, Dmitry Zabezhinsky, Markus Fischer, Aline Zimmer

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 30% of its field
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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. N-Lactoyl Amino Acids: Emerging Biomarkers in Metabolism and Disease.Diabetes/metabolism research and reviews · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. 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

9 authors at 2 institutions in 2 countries.

Corinna SchmidtMerck Life Science, Upstream R&D, Darmstadt, Germany.
Maria WehslingMerck Life Science, Upstream R&D, Darmstadt, Germany.
Maxime Le MignonMerck Life Science, Upstream R&D, Darmstadt, Germany.
Gregor WilleMerck Life Science, Process Development, Buchs, Switzerland.
Yannick ReyMerck Life Science, Process Development, Buchs, Switzerland.
Alisa SchnellbaecherMerck Life Science, Upstream R&D, Darmstadt, Germany.
Dmitry ZabezhinskyMerck Life Science, Upstream R&D, Darmstadt, Germany.
Markus FischerMerck Life Science, Process Development, Buchs, Switzerland.
Aline ZimmerMerck Life Science, Upstream R&D, Darmstadt, Germany.ORCID 0000-0003-0279-4863
Merck (Germany) · DEMerck Serono (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increasing demands for protein-based therapeutics such as monoclonal antibodies, fusion proteins, bispecific molecules, and antibody fragments require researchers to constantly find innovative solutions. To increase yields and decrease costs of next generation bioprocesses, highly concentrated cell culture media formulations are developed but often limited by the low solubility of amino acids such as tyrosine, cystine, leucine, and isoleucine, in particular at physiological pH. This study sought to investigate highly soluble and bioavailable derivatives of leucine and isoleucine that are applicable for fed-batch processes. N-lactoyl-leucine and N-lactoyl-isoleucine sodium salts were tested in cell culture media and proved to be beneficial to increase the overall solubility of cell culture media formulations. These modified amino acids proved to be bioavailable for various Chinese hamster ovary (CHO) cells and were suitable for replacement of canonical amino acids in cell culture feeds. The quality of the final recombinant protein was studied in bioprocesses using the derivatives, and the mechanism of cleavage was investigated in CHO cells. Altogether, both N-lactoyl amino acids represent an advantageous alternative to canonical amino acids to develop highly concentrated cell culture media formulations to support next generation bioprocesses.

Indexed as

Cell Culture TechniquesCulture MediaIsoleucineLeucineAnimalsAntibodies, MonoclonalCHO CellsCricetulusRecombinant ProteinsAntibodies, MonoclonalCulture MediaIsoleucineLeucineRecombinant Proteinsbioprocessescell culture mediaenzymatic cleavagelactoyl- (iso)leucinesolubility

Identifiers

PMID33738790
PMCPMC8453549
OpenAlexW3137654839

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.