Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Joint BioEnergy Institute, Emeryville, CA, 94608, USA.
J Ind Microbiol Biotechnol. 2018 Jul;45(7):621-633. doi: 10.1007/s10295-018-2021-9. Epub 2018 Feb 9.
Complex reduced polyketides represent the largest class of natural products that have applications in medicine, agriculture, and animal health. This structurally diverse class of compounds shares a common methodology of biosynthesis employing modular enzyme systems called polyketide synthases (PKSs). The modules are composed of enzymatic domains that share sequence and functional similarity across all known PKSs. We have used the nomenclature of synthetic biology to classify the enzymatic domains and modules as parts and devices, respectively, and have generated detailed lists of both. In addition, we describe the chassis (hosts) that are used to assemble, express, and engineer the parts and devices to produce polyketides. We describe a recently developed software tool to design PKS system and provide an example of its use. Finally, we provide perspectives of what needs to be accomplished to fully realize the potential that synthetic biology approaches bring to this class of molecules.
复杂还原聚酮类化合物是应用于医学、农业和动物健康领域的最大类天然产物,其结构多样,其生物合成方法采用模块化酶系统,称为聚酮合酶(PKSs)。这些模块由具有序列和功能相似性的酶域组成,这些酶域在所有已知的 PKSs 中都存在。我们使用合成生物学的命名法将酶域和模块分别分类为部件和设备,并分别生成了详细的列表。此外,我们还描述了用于组装、表达和工程化这些部件和设备以生产聚酮类化合物的底盘(宿主)。我们描述了一个最近开发的软件工具来设计 PKS 系统,并提供了一个使用示例。最后,我们提供了一些观点,说明了要充分发挥合成生物学方法在这一类分子上的潜力,需要完成哪些工作。