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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain elongation
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Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain elongation

机译:重新编程6-脱氧赤藓醇B合酶的模块以迭代链延长

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摘要

Multimodular polyketide synthases (PKSs) have an assembly line architecture in which a set of protein domains, known as a module,participates in one round of polyketide chain elongation and associated chemical modifications, after which the growing chain is translocated to the next PKS module. The ability to rationally reprogram these assembly lines to enable efficient synthesis of new polyketide antibiotics has been a long-standing goal in natural products biosynthesis. We have identified a ratchet mechanism that can explain the observed unidirectional translocation of the growing polyketide chain along the 6-deoxyerythronolide B synthase.As a test of this model, module 3 of the 6-deoxyerythronolide B synthase has been reengineered to catalyze two successive rounds of chain elongation. Our results suggest that high selectivity has been evolutionary programmed at three types of protein-protein interfaces that are present repetitively along naturally occurring PKS assembly lines.
机译:多模块聚酮化合物合酶(PKS)具有装配线体系结构,其中一组蛋白质域(称为模块)参与一轮聚酮化合物链的延伸和相关的化学修饰,然后将增长的链转移到下一个PKS模块中。合理地重新编程这些装配线以能够有效合成新的聚酮类抗生素的能力一直是天然产物生物合成中的长期目标。我们已经确定了一种棘轮机制,可以解释观察到的增长的聚酮化合物链沿6-脱氧赤藓醇B合酶的单向易位。作为对该模型的测试,已将6-脱氧赤藓醇B合酶的模块3重新设计为催化两个连续的回合链伸长率。我们的结果表明,高选择性已经进化为沿着天然存在的PKS装配线重复出现的三种蛋白质-蛋白质界面。

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    Departments of Chemistry Stanford University, Stanford, CA 94305;

    Chemical Engineering, Stanford University, Stanford, CA 94305;

    Departments of Chemistry Stanford University, Stanford, CA 94305;

    Departments of Chemistry Stanford University, Stanford, CA 94305;

    Chemical Engineering, Stanford University, Stanford, CA 94305;

    Department of Chemistry, Brown University, Box H,Providence, Rl 02912-9108;

    Departments of Chemistry Stanford University, Stanford, CA 94305 Chemical Engineering, Stanford University, Stanford, CA 94305 Department of Biochemistry, Stanford University, Stanford, CA 94305;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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