In vivo production of pederin by labrenzin pathway expansion

Dina Kačar; Carmen Schleissner; Librada M Cañedo; Pilar Rodríguez; Fernando de la Calle; Carmen Cuevas; Beatriz Galán; José Luis García

doi:10.1016/j.mec.2022.e00198

In vivo production of pederin by labrenzin pathway expansion

Metab Eng Commun. 2022 Apr 25:14:e00198. doi: 10.1016/j.mec.2022.e00198. eCollection 2022 Jun.

Authors

Dina Kačar¹, Carmen Schleissner², Librada M Cañedo², Pilar Rodríguez², Fernando de la Calle², Carmen Cuevas², Beatriz Galán¹, José Luis García¹

Affiliations

¹ Department of Microbial and Plant Biotechnology, Centro de Investigaciones Biológicas, Agencia Estatal Consejo Superior de Investigaciones Científicas, Madrid, Spain.
² Research and Development Department, PharmaMar S.A, Madrid, Spain.

Abstract

Pederin is a potent polyketide toxin that causes severe skin lesions in humans after contact with insects of genus Paederus. Due to its potent anticancer activities, pederin family compounds have raised the interest of pharmaceutical industry. Despite the extensive studies on the cluster of biosynthetic genes responsible for the production of pederin, it has not yet been possible to isolate and cultivate its bacterial endosymbiont producer. However, the marine bacterium Labrenzia sp. PHM005 was recently reported to produce labrenzin, the closest pederin analog. By cloning a synthetic pedO gene encoding one of the three O-methyltraferase of the pederin cluster into Labrenzia sp. PHM005 we have been able to produce pederin for the first time by fermentation in the new recombinant strain.