Admiraal Suzanne J, Khosla Chaitan, Walsh Christopher T
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
J Am Chem Soc. 2003 Nov 12;125(45):13664-5. doi: 10.1021/ja0379060.
A nonribosomal peptide synthetase (NRPS) loading module and a polyketide synthase (PKS) elongation module catalyze the preliminary steps in the biosynthesis of the rifamycin antibiotics. A benzoate molecule is covalently attached to the phosphopantetheine arm of the thiolation domain of the loading module when its reaction partner methylmalonyl-CoA is absent. Occupancy of the thiolation domain of the elongation module by a methylmalonyl moiety appears to trigger intermodular transfer of benzoate to the ketosynthase domain of the elongation module. This transthiolation event is fast relative to the initial loading of benzoate onto the loading module. It will be of interest to determine if these results are generally true for intermodular acyl transfer in other NRPS-PKS and PKS assembly lines.
非核糖体肽合成酶（NRPS）装载模块和聚酮合酶（PKS）延伸模块催化利福霉素抗生素生物合成的初步步骤。当反应伙伴甲基丙二酰辅酶A不存在时，苯甲酸分子会共价连接到装载模块硫醇化结构域的磷酸泛酰巯基乙胺臂上。延伸模块硫醇化结构域被甲基丙二酰部分占据似乎会触发苯甲酸向延伸模块酮合成酶结构域的模块间转移。相对于苯甲酸最初装载到装载模块上，这种硫醇转移事件发生得很快。确定这些结果对于其他NRPS-PKS和PKS装配线中的模块间酰基转移是否普遍成立将是很有意义的。
