Assembly-line polyketide synthases (PKSs) are among the most complex protein machineries known in nature, responsible for the biosynthesis of numerous compounds used in the clinic. Their present-day diversity is the result of an evolutionary path that has involved the emergence of a multimodular architecture and further diversification of assembly-line PKSs. In this review, we provide an overview of previous studies that investigated PKS evolution and propose a model that challenges the currently prevailing view that gene duplication has played a major role in the emergence of multimodularity. We also analyze the ensemble of orphan PKS clusters sequenced so far to evaluate how large the entire diversity of assembly-line PKS clusters and their chemical products could be. Finally, we examine the existing techniques to access the natural PKS diversity in natural and heterologous hosts and describe approaches to further expand this diversity through engineering.

中文翻译：

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装配线聚酮化合物合成酶的演变和多样性。

装配线聚酮合酶（PKS）是自然界已知的最复杂的蛋白质机器之一，负责临床使用的多种化合物的生物合成。它们如今的多样性是进化路径的结果，该进化路径涉及多模块架构的出现和装配线 PKS 的进一步多样化。在这篇综述中，我们概述了之前研究 PKS 进化的研究，并提出了一个模型，挑战了目前流行的观点，即基因重复在多模块性的出现中发挥了重要作用。我们还分析了迄今为止测序的孤儿 PKS 簇的整体，以评估装配线 PKS 簇及其化学产品的整体多样性有多大。最后，我们研究了获取天然和异源宿主中天然 PKS 多样性的现有技术，并描述了通过工程进一步扩展这种多样性的方法。