Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates
Abstract Pederin‐family polyketides today constitute a group of more than 30 molecules being produced as natural products by different microorganisms across multitude of ecological niches. They are mostly known for their extreme cytotoxic activity and the decades of long exploration as potential ant...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Microbial Biotechnology |
| Online Access: | https://doi.org/10.1111/1751-7915.14355 |
| _version_ | 1797333536110280704 |
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| author | Dina Kačar Librada M. Cañedo Pilar Rodríguez Carmen Schleissner Fernando de laCalle José Luis García Beatriz Galán |
| author_facet | Dina Kačar Librada M. Cañedo Pilar Rodríguez Carmen Schleissner Fernando de laCalle José Luis García Beatriz Galán |
| author_sort | Dina Kačar |
| collection | DOAJ |
| description | Abstract Pederin‐family polyketides today constitute a group of more than 30 molecules being produced as natural products by different microorganisms across multitude of ecological niches. They are mostly known for their extreme cytotoxic activity and the decades of long exploration as potential antitumor drugs. The difference in their potency and biological activity lies in the tailoring modifications of the core molecule. Despite the isolation of many pederin‐like molecules until the date, only marine bacterium Labrenzia sp. PHM005 was reported as a cultivable producer and able to be genetically modified. Here, we study the role of tailoring enzymes from the lab gene cluster responsible for methylation and hydroxylation of labrenzin core molecule. We managed to produce a spectrum of differently tailored labrenzin analogs for the development of future drugs. This work constitutes one‐step forward in understanding the biosynthesis of pederin‐family polyketides and provides the tools to modify and overproduce these anticancer drugs in a‐la‐carte manner in Labrenzia sp. PHM005, but also in other producers in the future. |
| first_indexed | 2024-03-08T08:06:23Z |
| format | Article |
| id | doaj.art-37a2d0bb3ec14a6cbdb5ce0655a69a5b |
| institution | Directory Open Access Journal |
| issn | 1751-7915 |
| language | English |
| last_indexed | 2024-03-08T08:06:23Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Microbial Biotechnology |
| spelling | doaj.art-37a2d0bb3ec14a6cbdb5ce0655a69a5b2024-02-02T10:34:50ZengWileyMicrobial Biotechnology1751-79152024-01-01171n/an/a10.1111/1751-7915.14355Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediatesDina Kačar0Librada M. Cañedo1Pilar Rodríguez2Carmen Schleissner3Fernando de laCalle4José Luis García5Beatriz Galán6Department of Microbial and Plant Biotechnology, Centro de Investigaciones Biológicas Margarita Salas Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC) Madrid SpainResearch and Development Department PharmaMar S.A. Madrid SpainResearch and Development Department PharmaMar S.A. Madrid SpainUnolabManufacturing Madrid SpainResearch and Development Department PharmaMar S.A. Madrid SpainDepartment of Microbial and Plant Biotechnology, Centro de Investigaciones Biológicas Margarita Salas Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC) Madrid SpainDepartment of Microbial and Plant Biotechnology, Centro de Investigaciones Biológicas Margarita Salas Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC) Madrid SpainAbstract Pederin‐family polyketides today constitute a group of more than 30 molecules being produced as natural products by different microorganisms across multitude of ecological niches. They are mostly known for their extreme cytotoxic activity and the decades of long exploration as potential antitumor drugs. The difference in their potency and biological activity lies in the tailoring modifications of the core molecule. Despite the isolation of many pederin‐like molecules until the date, only marine bacterium Labrenzia sp. PHM005 was reported as a cultivable producer and able to be genetically modified. Here, we study the role of tailoring enzymes from the lab gene cluster responsible for methylation and hydroxylation of labrenzin core molecule. We managed to produce a spectrum of differently tailored labrenzin analogs for the development of future drugs. This work constitutes one‐step forward in understanding the biosynthesis of pederin‐family polyketides and provides the tools to modify and overproduce these anticancer drugs in a‐la‐carte manner in Labrenzia sp. PHM005, but also in other producers in the future.https://doi.org/10.1111/1751-7915.14355 |
| spellingShingle | Dina Kačar Librada M. Cañedo Pilar Rodríguez Carmen Schleissner Fernando de laCalle José Luis García Beatriz Galán Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates Microbial Biotechnology |
| title | Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates |
| title_full | Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates |
| title_fullStr | Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates |
| title_full_unstemmed | Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates |
| title_short | Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates |
| title_sort | tailoring modifications in labrenzin synthesis a la carte production of pathway intermediates |
| url | https://doi.org/10.1111/1751-7915.14355 |
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