In vivo production of pederin by labrenzin pathway expansion

Kačar, Dina; Schleissner, Carmen; Cañedo, Librada M.; Rodríguez, Pilar; Calle, Fernando; Cuevas, Carmen; Galán, Beatriz; García, José L.

doi:10.1016/j.mec.2022.e00198

Cited by 3 publications

(6 citation statements)

References 21 publications

(28 reference statements)

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“…Plasmid pSEVA338 was used as an expression system for the mutation complementation with the functional genes. The construction of pSEVA338_ lab6 , pSEVA338_ lab16 , and pSEVA338_ lab6_lab16 was as described (Kačar et al, 2022 ). The lab7 and lab8 genes were PCR amplified and cloned in pSEVA338 using Sac I and Spe I restriction sites.…”

Section: Methodsmentioning

confidence: 99%

“…Plasmid DNA transformation and clone selection of the mutant strains carrying in‐trans functional genes for the purpose of mutation complementation were performed as described in a previous study (Kačar et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…The extraction and the following HPLC/MS analysis of labrenzin and newly identified intermediates procedures are as described in the previous study (Kačar et al, 2022 ). The isolation and purification of labrenzin for the structural elucidation are performed in PharmaMar as previously described (Schleissner et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

“…The early studies on pederin gene cluster proposed a position‐specific methylation for each methyltransferase (MT) encoded in the pederin ( ped ) gene cluster (Piel, 2002 ; Zimmermann et al, 2009 ). Ped cluster comprises three MTs (PedA, PedE and PedO) while lab cluster has only two MTs (Lab6 and Lab16; Kačar et al, 2019 , 2022 ; Piel, 2002 ; Piel, Hui, et al, 2004 ; Piel, Wen, et al, 2004 ). Moreover, compared with pederin that has four methoxy groups, labrenzin has only three methoxy groups, lacking the 18‐ O ‐methylation.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the in vivo expression of PedO in Labrenzia sp. PHM005 reported the production of pederin (Kačar et al, 2022 ), thus leaving the MTs Lab6 and Lab16 to be functionally characterized in the labrenzin and pederin pathways.…”

Section: Introductionmentioning

confidence: 99%

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Tailoring modifications in labrenzin synthesis: a‐la‐carte production of pathway intermediates

Kačar,

Cañedo,

Rodríguez

et al. 2023

Microbial Biotechnology

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%