Cortes J, Wiesmann K E, Roberts G A, Brown M J, Staunton J, Leadlay P F
Cambridge Centre for Molecular Recognition, University of Cambridge, UK.
Science. 1995 Jun 9;268(5216):1487-9. doi: 10.1126/science.7770773.
Macrocyclic polyketides exhibit an impressive range of medically useful activities, and there is great interest in manipulating the genes that govern their synthesis. The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, has been modified by repositioning of a chain-terminating cyclase domain to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension. The resulting mutant markedly accelerates formation of the predicted triketide lactone, compared to a control in which the repositioned domain is inactive. Repositioning of the cyclase should be generally useful for redirecting polyketide synthesis to obtain polyketides of specified chain lengths.
大环聚酮类化合物展现出一系列令人瞩目的医学应用活性，人们对操控其合成相关基因有着浓厚兴趣。糖多孢红霉菌的6-脱氧红霉内酯B合酶（DEBS）负责合成抗生素红霉素A的苷元核心，通过将链终止环化酶结构域重新定位到DEBS1（催化聚酮链前两轮延伸的多酶）的羧基末端，对其进行了改造。与重新定位的结构域无活性的对照相比，所得突变体显著加速了预测的三酮内酯的形成。环化酶的重新定位对于重新引导聚酮类化合物的合成以获得特定链长的聚酮类化合物通常应是有用的。
