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bioRxiv · 10.1101/2024.10.13.616080

Heterologous expression and optimization of fermentation conditions for recombinant ikarugamycin production

Evers, J. K.·Gloeckle, A.·Wiegand, M.·Schuler, S.·Einsiedler, M.·Gulder, T.
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Abstract

Ikarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis. It is therefore used as a tool compound to study diverse biological processes. However, ikarugamycin commercial prices are very high, with up to 1300 {euro} per 1 mg, thus limiting its application. We therefore set out to develop a high-yielding recombinant production platform of ikarugamycin by screening different expression vectors, recombinant host strains, and cultivation conditions. Overall, this has led to overproduction levels of more than 100 mg/L, which, together with a straightforward purification protocol, establishes biotechnological access to affordable ikarugamycin enabling its increased use in biomedical research in the future.

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Evers, J. K., Gloeckle, A., Wiegand, M., Schuler, S., Einsiedler, M., Gulder, T.. 2024-10-15. Heterologous expression and optimization of fermentation conditions for recombinant ikarugamycin production. https://doi.org/10.1101/2024.10.13.616080

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