PKSI-AT结构域及在组合生物合成研究中的应用

I型聚酮合酶（PKSI）的模块型分子结构组织方式非常适合于组合生物合成研究.结构域和模块通过二级组织方式构成了PKSI的催化单元，其它结构多肽则作为“支架”.在“支架”上对结构域和模块两个水平进行突变、替换、插入、缺失等基因操作形成重组PKS，可以理性设计并获得复杂多样的新活性或高活性的聚酮化合物.利用PKSI进行组合生物合成以期获得新聚酮化合物的研究迄今已有约25年，但是目前仍不能够对PKS进行完美的理性设计，快速合成目标活性的新聚酮化合物.PKS中的酰基转移酶结构域的研究在PKS的组合生物合成研究中一直发挥着重要作用.本文结合本课题组的研究基础，对AT结构域的结构、功能及在组合生物合成研究中的最新研究成果作以分析总结.

Type I Polyketide Synthase Acyltransferase Domain and Its Application in Combinatorial Biosynthesis

The modular organization of type I polyketide synthase makes it suitable for the study on combinatorial biosynthesis. Through a striking two level arrangement, domains and modules constitute the catalytic units of type I PKS. In the rest structural polypeptides, serving as scaffolds, mutation, substitution, insertion, and deletion of domains or modules on the two levels can be achieved through genetic manipulation thereby resulting in production of a variety of rationally designed polyketides with novel or higher activities. It has been about twenty five years since the type I PKS was employed in the study on combinatorial biosynthesis for novel polyketides, but the study on type I PKS can not yet make perfectly rational designation and quick production of novel polyketides. Studies on acyltransferase domain (AT) of type I PKS play an important role in the PKS combinatorial biosynthesis. In this review, we focus on the function of AT domain and its role in combinatorial biosynthesis, and provide a brief overview on the latest studies.