Description: Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440

This title appears in the Scientific Report : 2018

Preparation of Cyclic Prodiginines by Mutasynthesis in Pseudomonas putida KT2440

Prodiginines are a group of naturally occurring pyrrole alkaloids produced by various microorganisms and known for their broad biological activities. The production of nature‐inspired cyclic prodiginines was enabled by combining organic synthesis with a mutasynthesis approach based on the GRAS (gene...

Personal Name(s):	Klein, Andreas Sebastian
	Brass, Hannah Ursula Clara / Klebl, David Paul / Classen, Thomas / Loeschcke, Anita / Drepper, Thomas / Sievers, Sonja / Jaeger, Karl-Erich / Pietruszka, Jörg (Corresponding author)
Contributing Institute:	Institut für Molekulare Enzymtechnologie (HHUD); IMET Biotechnologie; IBG-1 Institut für Bioorganische Chemie (HHUD); IBOC
Published in:	ChemBioChem, 19 (2018) 14, S. 1545 - 1552
Imprint:	Weinheim Wiley-VCH 2018
PubMed ID:	29719131
DOI:	10.1002/cbic.201800154
Document Type:	Journal Article
Research Program:	Innovative Synergisms
	Publikationsportal JuSER

Please use the identifier: http://dx.doi.org/10.1002/cbic.201800154 in citations.

Prodiginines are a group of naturally occurring pyrrole alkaloids produced by various microorganisms and known for their broad biological activities. The production of nature‐inspired cyclic prodiginines was enabled by combining organic synthesis with a mutasynthesis approach based on the GRAS (generally recognized as safe) certified host strain Pseudomonas putida KT2440. The newly prepared prodiginines exerted antimicrobial effects against relevant alternative biotechnological microbial hosts whereas P. putida itself exhibited remarkable tolerance against all tested prodiginines, thus corroborating the bacterium's exceptional suitability as a mutasynthesis host for the production of these cytotoxic secondary metabolites. Moreover, the produced cyclic prodiginines proved to be autophagy modulators in human breast cancer cells. One promising cyclic prodiginine derivative stood out, being twice as potent as prodigiosin, the most prominent member of the prodiginine family, and its synthetic derivative obatoclax mesylate.