ACS Chem Biol. 2011 May 20;6(5):413-8. doi: 10.1021/cb200004k. Epub 2011 Feb 22.
Type II polyketide synthases are biosynthetic enzymatic pathways responsible for the production of complex aromatic natural products with important biological activities. In these systems, biosynthetic intermediates are covalently bound to a small acyl carrier protein that associates with the synthase enzymes and delivers the bound intermediate to each active site. In the closely related fatty acid synthases of bacteria and plants, the acyl carrier protein acts to sequester and protect attached intermediates within its helices. Here we investigate the type II polyketide synthase acyl carrier protein from the actinorhodin biosynthetic pathway and demonstrate its ability to internalize the tricyclic, polar molecule emodic acid. Elucidating the interaction of acyl carrier proteins with bound analogues resembling late-stage intermediates in the actinorhodin pathway could prove valuable in efforts to engineer these systems toward rational design and biosynthesis of novel compounds.
II 型聚酮合酶是生物合成酶途径,负责产生具有重要生物活性的复杂芳香天然产物。在这些系统中,生物合成中间体与小酰基载体蛋白共价结合,该蛋白与合酶酶结合,并将结合的中间体递送到每个活性位点。在细菌和植物中密切相关的脂肪酸合酶中,酰基载体蛋白的作用是将附着的中间体隔离并保护在其螺旋内。在这里,我们研究了来自放线紫红素生物合成途径的 II 型聚酮合酶酰基载体蛋白,并证明了它能够内化三环、极性分子大黄酸。阐明酰基载体蛋白与类似放线紫红素途径中晚期中间体的结合类似物的相互作用,对于通过理性设计和生物合成新型化合物来工程化这些系统可能是有价值的。