Natural product biosynthesis (NPB) is the Panda's Thumb of evolutionary biochemistry. Arm races between organisms, and ever-changing environments, result in relentless innovation. This review focusses on enzyme evolution in NPB. First, we review cases of de novo emergence, whereby a completely new enzymatic activity arose in a ligand-binding protein, or a new enzyme emerged including a completely new scaffold. Second, we briefly review the current models for enzyme evolution, and how they explain the inherent promiscuity of NPB enzymes and their tendency to produce multiple related products. We thus suggest that NPB enzymes a priori evolved to generate a specific product; they are, however, trapped in a multifunctional, generalist evolutionary state and thereby produce a diversity of products.

中文翻译：

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天然产物生物合成中的酶进化：目标导向还是多样性导向？

天然产物生物合成 (NPB) 是进化生物化学的大拇指。生物体之间的军备竞赛和不断变化的环境导致了无情的创新。本综述重点关注 NPB 中的酶进化。首先，我们回顾了从头出现的案例，即在配体结合蛋白中出现了全新的酶活性，或者出现了包括全新支架的新酶。其次，我们简要回顾了当前的酶进化模型，以及它们如何解释 NPB 酶的内在混杂及其产生多种相关产品的趋势。因此，我们建议 NPB 酶先验进化以产生特定的产物；然而，它们被困在一个多功能的、通用的进化状态，从而生产出多样化的产品。