Evidence map›Paper›PMID 35643529›Full record

ArticleMicrobial cell factories2022

Optimization of the production process for the anticancer lead compound illudin M: improving titers in shake-flasks.

Lillibeth Chaverra-Muñoz, Theresa Briem, Stephan Hüttel

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Lillibeth Chaverra-MuñozDepartment of Microbial Drugs, Helmholtz Centre for Infection Research, Brunswick, Germany.
Theresa BriemDepartment of Microbial Drugs, Helmholtz Centre for Infection Research, Brunswick, Germany.
Stephan HüttelDepartment of Microbial Drugs, Helmholtz Centre for Infection Research, Brunswick, Germany. Stephan.Huettel@outlook.com.
Helmholtz Centre for Infection Research · DEGerman Center for Infection Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe fungal sesquiterpenes Illudin M and S are important base molecules for the development of new anticancer agents due to their strong activity against some resistant tumor cell lines. Due to nonspecific toxicity of the natural compounds, improvement of the pharmacophore is required. A semisynthetic derivative of illudin S (Irofulven) entered phase II clinical trials for the treatment of castration-resistant metastatic prostate cancer. Several semisynthetic illudin M derivatives showed increased in vitro selectivity and improved therapeutic index against certain tumor cell lines, encouraging further investigation. This requires a sustainable supply of the natural compound, which is produced by Basidiomycota of the genus Omphalotus. We aimed to develop a robust biotechnological process to deliver illudin M in quantities sufficient to support medicinal chemistry studies and future preclinical and clinical development. In this study, we report the initial steps towards this goal.

resultsAfter establishing analytical workflows, different culture media and commercially available Omphalotus strains were screened for the production of illudin M.Omphalotus nidiformis cultivated in a medium containing corn steep solids reached ~ 38 mg L

conclusionAfter strict standardization of seed-preparation and cultivation parameters, a combination of experimental design, empirical trials and additional supply of limiting biosynthetic precursors, led to a highly reproducible process in shake flasks with high titers of illudin M. These findings are the base for further work towards a scalable biotechnological process for a stable illudin M supply.

Indexed as

GlucoseCell Line, TumorPolycyclic SesquiterpenesGlucoseilludin MPolycyclic SesquiterpenesAcetateAnti-cancer agentsBasidiomycotaBioprocess optimizationFed-batchFungal secondary metabolitesIrofulvenMedium developmentNatural productsShake-flaskSmall-scale

Identifiers

PMID35643529
PMCPMC9148526
OpenAlexW4281646011

What OpenQuestion holds

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LicenceCC BY
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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.