Microbiology Doctoral Training Program, University of Wisconsin, Madison, WI 53705, USA.
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13498-503. doi: 10.1073/pnas.1106919108. Epub 2011 Aug 8.
Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases and have emerged as promising drug leads for both antibacterial and antidiabetic therapies. Comparative analysis of the PTM and PTN biosynthetic machineries in Streptomyces platensis MA7327 and MA7339 revealed that the divergence of PTM and PTN biosynthesis is controlled by dedicated ent-kaurene and ent-atiserene synthases, the latter of which represents a new pathway for diterpenoid biosynthesis. The PTM and PTN biosynthetic machineries provide a rare glimpse at how secondary metabolic pathway evolution increases natural product structural diversity and support the wisdom of applying combinatorial biosynthesis methods for the generation of novel PTM and/or PTN analogues, thereby facilitating drug development efforts based on these privileged natural product scaffolds.
盘菌霉素（PTM）和盘菌素（PTN）是强效且选择性的细菌和哺乳动物脂肪酸合酶抑制剂，已成为抗菌和抗糖尿病治疗有前途的药物先导物。对链霉菌属中盘菌霉素（PTM）和盘菌素（PTN）生物合成机制的比较分析表明，PTM 和 PTN 生物合成的差异是由专用的 ent-贝壳杉烯和 ent-对贝壳杉烯合酶控制的，后者代表了二萜生物合成的新途径。PTM 和 PTN 生物合成机制为我们提供了一个难得的视角，了解二次代谢途径的进化如何增加天然产物结构多样性，并支持应用组合生物合成方法生成新型 PTM 和/或 PTN 类似物的智慧，从而促进基于这些特权天然产物支架的药物开发工作。
