To date little is known about the genetic background that drives the production and diversification of secondary metabolites in the Hypoxylaceae. With the recent availability of high-quality genome sequences for 13 representative species and one relative (Xylaria hypoxylon) we attempted to survey the diversity of biosynthetic pathways in these organisms to investigate their true potential as secondary metabolite producers. Manual search strategies based on the accumulated knowledge on biosynthesis in fungi enabled us to identify 783 biosynthetic pathways across 14 studied species, the majority of which were arranged in biosynthetic gene clusters (BGC). The similarity of BGCs was analysed with the BiG-SCAPE engine which organised the BGCs into 375 gene cluster families (GCF). Only ten GCFs were conserved across all of these fungi indicating that speciation is accompanied by changes in secondary metabolism. From the known compounds produced by the family members some can be directly correlated with identified BGCs which is highlighted herein by the azaphilone, dihydroxynaphthalene, tropolone, cytochalasan, terrequinone, terphenyl and brasilane pathways giving insights into the evolution and diversification of those compound classes. Vice versa, products of various BGCs can be predicted through homology analysis with known pathways from other fungi as shown for the identified ergot alkaloid, trigazaphilone, curvupallide, viridicatumtoxin and swainsonine BGCs. However, the majority of BGCs had no obvious links to known products from the Hypoxylaceae or other well-studied biosynthetic pathways from fungi. These findings highlight that the number of known compounds strongly underrepresents the biosynthetic potential in these fungi and that a tremendous number of unidentified secondary metabolites is still hidden. Moreover, with increasing numbers of genomes for further Hypoxylaceae species becoming available, the likelihood of revealing new biosynthetic pathways that encode new, potentially useful compounds will significantly improve. Reaching a better understanding of the biology of these producers, and further development of genetic methods for their manipulation, will be crucial to access their treasures.

中文翻译：

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真菌科 Hypoxylaceae 和 Xylaria hypoxylon 中的次生代谢物生物合成多样性。

迄今为止，人们对推动 Hypoxylaceae 次生代谢产物的产生和多样化的遗传背景知之甚少。随着最近 13 个代表性物种和 1 个亲属（Xylaria hypoxylon）的高质量基因组序列的可用性，我们试图调查这些生物体中生物合成途径的多样性，以研究它们作为次级代谢产物生产者的真正潜力。基于积累的真菌生物合成知识的手动搜索策略使我们能够识别 14 个研究物种中的 783 条生物合成途径，其中大部分排列在生物合成基因簇 (BGC) 中。BGC 的相似性用 BiG-SCAPE 引擎分析，该引擎将 BGC 组织成 375 个基因簇家族 (GCF)。所有这些真菌中只有 10 个 GCF 是保守的，这表明物种形成伴随着次级代谢的变化。从家族成员产生的已知化合物中，一些可以与已识别的 BGC 直接相关，本文通过 azaphilone、二羟基萘、托酚酮、细胞松弛素、terrequinone、三联苯和 Brasil 途径突出显示这些化合物类别的演变和多样化。反之亦然，如已鉴定的麦角生物碱、trigazaphilone、curvupallide、viridicatumtoxin 和 swainsonine BGCs 所示，可以通过同源性分析与来自其他真菌的已知途径预测各种 BGC 的产物。然而，大多数 BGC 与来自 Hypoxylaceae 的已知产物或其他经过充分研究的真菌生物合成途径没有明显的联系。这些发现强调，已知化合物的数量严重低估了这些真菌的生物合成潜力，并且仍然隐藏着大量未鉴定的次级代谢物。此外，随着更多地衣科物种的基因组数量的增加，揭示编码新的、潜在有用的化合物的新生物合成途径的可能性将显着提高。更好地了解这些生产者的生物学，并进一步开发操纵它们的遗传方法，对于获取它们的宝藏至关重要。随着更多地衣科物种的基因组数量的增加，揭示编码新的、潜在有用的化合物的新生物合成途径的可能性将显着提高。更好地了解这些生产者的生物学，并进一步开发操纵它们的遗传方法，对于获取它们的宝藏至关重要。随着更多地衣科物种的基因组数量的增加，揭示编码新的、潜在有用的化合物的新生物合成途径的可能性将显着提高。更好地了解这些生产者的生物学，并进一步开发操纵它们的遗传方法，对于获取它们的宝藏至关重要。