the polyketide to fatty acid transition in the evolution of animal lipid metabolism:the animal FAS-like PKSs

Animals use a distinct fatty acid synthase (FAS) most closely related to the type I polyketide synthase (PKS) enzymes. While FASs synthesize simple lipids, PKSs produce complex specialized metabolites. The evolutionary origin of the animal FAS, and its relationship to the diversity of PKSs, remain surprisingly mysterious despite the critical role of lipid synthesis in cellular metabolism. Previously, an enzyme EcPKS1 from sacoglossan molluscs was described that was closely related to animal FAS enzymes, but instead preformed PKS-like chemistry. A few other related enzymes were apparent in molluscs, mostly in the photosynthetic sacoglossans. Here, we asked whether such enzymes were limited to a small subset of species, and whether they might answer the mystery of the origin of animal lipid biosynthesis. We performed a sequence-based analysis, unexpectedly discovering a huge diversity of widespread EcPKS1-like enzymes that form a grade separating PKS from the animal FAS clade in phylogenetic analyses. PKSs and FASs are widespread among major animal phyla except for sponges and ctenophores, where they are apparently absent. Surprisingly, molluscs and arthropods contain abundant EcPKS1-like enzymes, correlated with their rich polyketide chemistry. Molluscan EcPKS1 relatives are associated with a lack of other defenses, consistent with the hypothesis that AFPKs provide a chemical defense for some lineages. By contrast, shelled molluscs (physically defended) generally contain PKSs instead. Arthropods have few or no PKSs, but their abundant EcPKS1-like enzymes contributed to their ecological and evolutionary success. For example, some of the genes found in the EcPKS1 clade were previously associated with cuticular hydrocarbon and pheromone biosynthesis. Based upon the biochemical, genetic, and phylogenetic features of these enzymes, we propose that they comprise a new family, the animal FAS-like PKSs (AFPKS). Although animal metabolism is well studied, surprising new metabolic enzyme classes such as AFPKs still await discovery and may be unrecognized drivers of hyperdiverse animal radiations including gastropods, beetles and spiders.

动物拥有一类独特的脂肪酸合酶（fatty acid synthase, FAS），其与I型聚酮合酶（type I polyketide synthase, PKS）类酶的亲缘关系最为密切。脂肪酸合酶负责合成简单脂质，而聚酮合酶则可产生复杂的特化代谢物。尽管脂质合成在细胞代谢中发挥着关键作用，但动物脂肪酸合酶的演化起源，以及它与聚酮合酶多样性之间的关联，至今仍充满未解之谜。此前，研究人员已在囊舌类软体动物中报道过一种名为EcPKS1的酶，该酶与动物脂肪酸合酶类酶亲缘关系紧密，却能发挥类似聚酮合酶的催化功能。此外在软体动物，尤其是具有光合能力的囊舌类物种中，还发现了少量其他与之相关的酶类。本研究旨在探究这类酶是否仅局限于少数物种，以及它们能否为解答动物脂质生物合成的起源之谜提供线索。我们通过基于序列的分析，意外发现了一类分布广泛、种类繁多的EcPKS1同源酶；系统发育分析显示，这类酶构成了一个介于聚酮合酶与动物脂肪酸合酶演化支之间的过渡类群。除海绵动物与栉水母动物外，脂肪酸合酶与聚酮合酶在各大动物门类中均有分布，而这两类酶在海绵和栉水母中似乎完全缺失。值得注意的是，软体动物与节肢动物中含有丰富的EcPKS1同源酶，这与其体内丰富的聚酮类化合物合成能力相契合。软体动物的EcPKS1同源酶往往伴随其他防御机制的缺失，这与“AFPKs可为部分动物类群提供化学防御”的假说相符。与之相对，具有物理防御结构的带壳软体动物通常仅含有聚酮合酶而非EcPKS1同源酶。节肢动物几乎不含聚酮合酶，但其丰富的EcPKS1同源酶却助力其实现了生态与演化上的成功。例如，EcPKS1演化支中的部分基因此前已被证实与表皮碳氢化合物及信息素的生物合成相关。基于这些酶的生化特性、遗传特征与系统发育关系，我们提出应当将其归为一个新的家族——动物脂肪酸合酶类聚酮合酶（animal FAS-like PKSs, AFPKS）。尽管动物代谢的研究已较为深入，但诸如AFPKs这类令人惊喜的新型代谢酶类仍有待发掘，它们或许正是包括腹足类、甲虫与蜘蛛在内的高度多样化动物类群辐射演化的未被认知的关键驱动因素。