Type III polyketide synthases (PKSs) produce secondary metabolites with diverse biological activities, including antimicrobials. While they have been extensively studied in plants and bacteria, only a handful of type III PKSs from fungi has been characterized in the last 15 years. The exploitation of fungal type III PKSs to produce novel bioactive compounds requires understanding the diversity of these enzymes, as well as of their biosynthetic pathways. Here, phylogenetic and reconciliation analyses of 522 type III PKSs from 1,193 fungal genomes revealed complex evolutionary histories with massive gene duplications and losses, explaining their discontinuous distribution in the fungal tree of life. In addition, horizontal gene transfer events from bacteria to fungi and, to a lower extent, between fungi, could be inferred. Ancestral gene duplication events have resulted in the divergence of eight phylogenetic clades. Especially, two clades show ancestral linkage and functional co-evolution between a type III PKS and a reducing PKS genes. Investigation of the occurrence of protein domains in fungal type III PKS predicted gene clusters highlighted the diversity of biosynthetic pathways, likely reflecting a large chemical landscape. Type III PKS genes are most often located next to genes encoding cytochrome P450s, MFS transporters and transcription factors, defining ancestral core gene clusters. This analysis also allowed predicting gene clusters for the characterized fungal type III PKSs and provides working hypotheses for the elucidation of the full biosynthetic pathways. Altogether, our analyses provide the fundamental knowledge to motivate further characterization and exploitation of fungal type III PKS biosynthetic pathways.

中文翻译：

---

真菌中III型聚酮化合物合酶的进化历史。

III型聚酮化合物合酶（PKS）产生具有多种生物活性的次级代谢产物，包括抗微生物剂。尽管已在植物和细菌中对它们进行了广泛的研究，但在过去的15年中，仅对少数几种真菌的III型PKS进行了表征。利用真菌III型PKS产生新的生物活性化合物需要了解这些酶的多样性及其生物合成途径。在这里，对来自1,193个真菌基因组的522种III型PKS的系统发育和和解分析揭示了具有大量基因重复和损失的复杂进化历史，解释了它们在真菌生命树中的不连续分布。此外，可以推断出从细菌到真菌的水平基因转移事件，以及在真菌之间水平转移的事件。祖先的基因复制事件导致了八个进化系统进化枝的分歧。特别地，两个进化枝显示了III型PKS和还原性PKS基因之间的祖先连锁和功能共同进化。对真菌III型PKS预测的基因簇中蛋白质结构域的发生进行的调查突出了生物合成途径的多样性，可能反映了较大的化学景观。III型PKS基因最常位于编码细胞色素P450，MFS转运蛋白和转录因子的基因旁边，从而定义了祖先核心基因簇。该分析还可以预测特征化的III型真菌PKS的基因簇，并为阐明完整的生物合成途径提供了可行的假设。共，