Activating hybrid modular interfaces in synthetic polyketide synthases by cassette replacement of ketosynthase domains
Activating hybrid modular interfaces in synthetic polyketide synthases by cassette replacement of ketosynthase domains
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DOI：
10.1016/j.chembiol.2006.02.011
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发表时间：
2006-05-01
影响因子：
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通讯作者：
Santi, Daniel V.
中科院分区：
文献类型：
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作者：
Chandran, Sunil S.;Menzella, Hugo G.;Santi, Daniel V.
聚酮化合物合酶模块的非天然组合通常不能制备聚酮化合物产物。这些失败的原因可能是复杂的，尚不能进行合理的纠正。一种可能的解释是酮合酶（KS）结构域不能延伸上游模块提供给它的酮化合物。因此，我们通过以组合方式交换受体模块的KS结构域并将这些嵌合模块与自然地与移植的KS相互作用的酮供体模块共表达来解决这个问题。这种方法在激活以前非生产性的双模块组合方面非常成功，并且结果预示着正在进行的分子工具的开发，以设计和生产新型聚酮化合物。
Unnatural combinations of polyketide synthase modules often fail to make a polyketide product. The causes of these failures are likely complex and are not yet amenable to rational correction. One possible explanation is the inability of the ketosynthase (KS) domain to extend the ketide donated to it by the upstream module. We therefore addressed the problem by exchanging KS domains of the acceptor module in a combinatorial fashion and coexpressing these chimeric modules with ketide-donor modules that naturally interact with the transplanted KS. This approach was remarkably successful in activating previously unproductive bimodular combinations, and the results augur well for the ongoing development of molecular tools to design and produce novel polyketides.