This title appears in the Scientific Report :
2017
Please use the identifier:
http://dx.doi.org/10.1021/acssynbio.7b00099 in citations.
New Prodigiosin Derivatives Obtained by Mutasynthesis in Pseudomonas putida
New Prodigiosin Derivatives Obtained by Mutasynthesis in Pseudomonas putida
The deeply red-colored natural compound prodigiosin is a representative of the prodiginine alkaloid family, which possesses bioactivities as antimicrobial, antitumor, and antimalarial agents. Various bacteria including the opportunistic human pathogen Serratia marcescens and different members of the...
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Personal Name(s): | Klein, Andreas |
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Domroese, Andreas / Bongen, Patrick / Brass, Hannah / Classen, Thomas / Loeschcke, Anita / Drepper, Thomas / Laraia, L. / Sievers, S. / Jaeger, Karl-Erich / Pietruszka, Jörg (Corresponding author) | |
Contributing Institute: |
Biotechnologie; IBG-1 Institut für Bioorganische Chemie (HHUD); IBOC Institut für Molekulare Enzymtechnologie (HHUD); IMET |
Published in: | ACS synthetic biology, 6 (2017) S. 1757-1765 |
Imprint: |
Washington, DC
ACS
2017
|
DOI: |
10.1021/acssynbio.7b00099 |
PubMed ID: |
28505410 |
Document Type: |
Journal Article |
Research Program: |
Innovative Synergisms |
Publikationsportal JuSER |
The deeply red-colored natural compound prodigiosin is a representative of the prodiginine alkaloid family, which possesses bioactivities as antimicrobial, antitumor, and antimalarial agents. Various bacteria including the opportunistic human pathogen Serratia marcescens and different members of the Streptomycetaceae and Pseudoalteromonadaceae produce prodiginines. In addition, these microbes generally accumulate many structurally related alkaloids making efficient prodiginine synthesis and purification difficult and expensive. Furthermore, it is known that structurally different natural prodiginine variants display differential bioactivities. In the herein described mutasynthesis approach, 13 different derivatives of prodigiosin were obtained utilizing the GRAS (generally recognized as safe) classified strain Pseudomonas putida KT2440. Genetic engineering of the prodigiosin pathway together with incorporation of synthetic intermediates thus resulted in the formation of a so far unprecedented structural diversity of new prodiginine derivatives in P. putida. Furthermore, the formed products allow reliable conclusions regarding the substrate specificity of PigC, the final condensing enzyme in the prodigiosin biosynthesis pathway of S. marcescens. The biological activity of prodigiosin toward modulation of autophagy was preserved in prodiginine derivatives. One prodiginine derivative displayed more potent autophagy inhibitory activity than the parent compound or the synthetic clinical candidate obatoclax. |