当前位置：
X-MOL 学术
›
ACS Synth. Biol.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
New Prodigiosin Derivatives Obtained by Mutasynthesis in Pseudomonas putida
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2017-05-26 00:00:00 , DOI: 10.1021/acssynbio.7b00099 Andreas S. Klein , Andreas Domröse , Patrick Bongen , Hannah U. C. Brass , Thomas Classen 1 , Anita Loeschcke , Thomas Drepper , Luca Laraia , Sonja Sievers , Karl-Erich Jaeger 1 , Jörg Pietruszka 1
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2017-05-26 00:00:00 , DOI: 10.1021/acssynbio.7b00099 Andreas S. Klein , Andreas Domröse , Patrick Bongen , Hannah U. C. Brass , Thomas Classen 1 , Anita Loeschcke , Thomas Drepper , Luca Laraia , Sonja Sievers , Karl-Erich Jaeger 1 , Jörg Pietruszka 1
Affiliation
|
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.
中文翻译：
恶臭假单胞菌经突变合成获得的新神童衍生物
深红色的天然化合物prodigiosin是prodiginine生物碱家族的代表，该家族具有抗微生物剂，抗肿瘤剂和抗疟剂的生物活性。各种细菌，包括机会性人类病原体粘质沙雷氏菌和链霉菌科和假单胞菌科的不同成员产生奇迹 此外，这些微生物通常会积聚许多结构相关的生物碱，从而难以高效地进行地精胺的合成和纯化。此外，已知结构上不同的天然地黄嘌呤变体显示出不同的生物活性。在本文所述的突变合成方法中，利用GRAS（通常被认为是安全的）分类菌株恶臭假单胞菌KT2440获得了黄原菌素的13种不同衍生物。因此，prodigiosin途径的基因工程以及合成中间体的掺入导致恶臭假单胞菌中新的prodiginine衍生物形成了迄今为止前所未有的结构多样性。。此外，所形成的产物可提供关于PigC的底物特异性的可靠结论，PigC是marcescens的prodigiosin生物合成途径中的最终缩合酶。prodiginine衍生物保留了prodigiosin对自噬调节的生物学活性。一种prodiginine衍生物比母体化合物或合成的临床候选obatoclax表现出更强的自噬抑制活性。
更新日期：2017-05-26
中文翻译：
恶臭假单胞菌经突变合成获得的新神童衍生物
深红色的天然化合物prodigiosin是prodiginine生物碱家族的代表，该家族具有抗微生物剂，抗肿瘤剂和抗疟剂的生物活性。各种细菌，包括机会性人类病原体粘质沙雷氏菌和链霉菌科和假单胞菌科的不同成员产生奇迹 此外，这些微生物通常会积聚许多结构相关的生物碱，从而难以高效地进行地精胺的合成和纯化。此外，已知结构上不同的天然地黄嘌呤变体显示出不同的生物活性。在本文所述的突变合成方法中，利用GRAS（通常被认为是安全的）分类菌株恶臭假单胞菌KT2440获得了黄原菌素的13种不同衍生物。因此，prodigiosin途径的基因工程以及合成中间体的掺入导致恶臭假单胞菌中新的prodiginine衍生物形成了迄今为止前所未有的结构多样性。。此外，所形成的产物可提供关于PigC的底物特异性的可靠结论，PigC是marcescens的prodigiosin生物合成途径中的最终缩合酶。prodiginine衍生物保留了prodigiosin对自噬调节的生物学活性。一种prodiginine衍生物比母体化合物或合成的临床候选obatoclax表现出更强的自噬抑制活性。
京公网安备 11010802027423号