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Post-PKS enzyme complexes
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2019-08-13 , DOI: 10.1039/c9md00066f
Redding Gober 1, 2, 3, 4, 5 , Ryan Wheeler 1, 2, 3, 4, 5 , Jürgen Rohr 1, 2, 3, 4, 5
Affiliation  

Natural products are produced by bacteria, plants, and fungi and have yielded some of the most clinically active and widely used drugs available. Several of the natural products that are produced by type II PKSs have novel scaffolds or unique rearrangements that are, in large part, due to the post PKS enzymes. Protein–protein interactions between post-PKS tailoring enzymes hamper the use of combinatorial biosynthesis in the development of novel natural product-derived drugs. Several co-dependent post-PKS enzymes have been characterized in nature, but their significance in regards to complex formation and co-dependence has been largely overlooked. Here, we report an in-depth analysis of two such post-PKS pathways, gilvocarcin and mithramycin, for which indications exist to postulate multienzyme complexes to facilitate substrate protection and channeling.

中文翻译:

PKS后酶复合物

天然产物是由细菌,植物和真菌产生的,并产生了一些临床上最活跃和使用最广泛的药物。II型PKS生产的几种天然产物具有新颖的支架或独特的重排,这在很大程度上归因于PKS后的酶。PKS后修饰酶之间的蛋白质相互作用会阻碍新型生物天然药物开发中组合生物合成的应用。在自然界中已经表征了几种共同依赖的后PKS酶,但是在复杂形成和共同依赖方面,它们的重要性已被大大忽略。在这里,我们报告了对两种此类后PKS途径吉尔卡星和光神霉素的深入分析,
更新日期:2019-08-13
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