Fischer Manuel, Grininger Martin
Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.
Beilstein J Org Chem. 2017 Jun 21;13:1204-1211. doi: 10.3762/bjoc.13.119. eCollection 2017.
Megasynthases are large multienzyme proteins that produce a plethora of important natural compounds by catalyzing the successive condensation and modification of precursor units. Within the class of megasynthases, polyketide synthases (PKS) are responsible for the production of a large spectrum of bioactive polyketides (PK), which have frequently found their way into therapeutic applications. Rational engineering approaches have been performed during the last 25 years that seek to employ the "assembly-line synthetic concept" of megasynthases in order to deliver new bioactive compounds. Here, we highlight PKS engineering strategies in the light of the newly emerging structural information on megasynthases, and argue that fatty acid synthases (FAS) are and will be valuable objects for further developing this field.
巨型合成酶是一类大型多酶蛋白，通过催化前体单元的连续缩合和修饰来产生大量重要的天然化合物。在巨型合成酶类别中，聚酮合酶（PKS）负责合成多种具有生物活性的聚酮化合物（PK），这些聚酮化合物经常被应用于治疗领域。在过去25年里，人们开展了合理的工程方法，试图利用巨型合成酶的“装配线合成概念”来开发新的生物活性化合物。在此，我们根据关于巨型合成酶的最新结构信息，重点介绍聚酮合酶的工程策略，并认为脂肪酸合酶（FAS）过去是、将来也会是进一步发展该领域的有价值对象。
