Lee Alysha K, Welander Paula V
Department of Earth Systems Science, Stanford University, Stanford, California, USA.
J Bacteriol. 2025 Apr 17;207(4):e0049524. doi: 10.1128/jb.00495-24. Epub 2025 Mar 11.
Myxococcota is a phylum of sterol-producing bacteria. They exhibit a clade depth for sterol biosynthesis unparalleled in the bacterial domain and produce sterols of a biosynthetic complexity that rivals eukaryotes. Additionally, the sterol biosynthesis pathways found in this phylum have been proposed as a potential source for sterol biosynthesis in the last eukaryotic common ancestor, lending evolutionary importance to our understanding of this pathway in Myxococcota. However, sterol production has only been characterized in a few species, and outstanding questions about the evolutionary history of this pathway remain. Here, we identify two myxobacteria, and , capable of cholesterol biosynthesis. These two myxobacteria possess a cholesterol biosynthesis pathway that differs in both the ordering and enzymes involved in biosynthesis compared with , a myxobacterium previously demonstrated to produce cholesterol, as well as the canonical pathways found in eukaryotes. We characterize an alternative bacterial reductase responsible for performing C-24 reduction, further delineating bacterial cholesterol production from eukaryotes. Finally, we examine the distribution and phylogenetic relationships of sterol biosynthesis proteins across both cultured and uncultured Myxococcota species, providing evidence for multiple acquisition events and instances of both horizontal and vertical transfer at the family level. Altogether, this work further demonstrates the capacity of myxobacteria to synthesize eukaryotic sterols but with an underlying diversity in the biochemical reactions that govern sterol synthesis, suggesting a complex evolutionary history and refining our understanding of how myxobacterial cholesterol production relates to their eukaryotic counterparts.
Sterols are essential and ubiquitous lipids in eukaryotes, but their significance in bacteria is less understood. Sterol production in Myxococcota, a phylum of developmentally complex predatory bacteria, has provided insight into novel sterol biochemistry and prompted discussion regarding the evolution of this pathway within both the eukaryotic and bacterial domains. Here, we characterize cholesterol biosynthesis in two myxobacteria, providing evidence for distinct pathway organization and identifying a unique protein responsible for C-24 reduction. We couple these results with the phylogenomic analysis of sterol biosynthesis within Myxococcota, revealing a complicated evolutionary history marked by vertical and horizontal transfer. This suggests a mosaic acquisition of this pathway in Myxococcota and highlights the complex role myxobacteria may have had in sterol transfer to eukaryotes.
粘球菌门是一类能产生固醇的细菌。它们在细菌域中展现出了在固醇生物合成方面无与伦比的进化分支深度，并且能产生生物合成复杂性可与真核生物相媲美的固醇。此外，该门中发现的固醇生物合成途径被认为是最后一个真核生物共同祖先中固醇生物合成的潜在来源，这使得我们对粘球菌门中这一途径的理解具有了进化上的重要性。然而，仅在少数物种中对固醇产生进行了表征，关于该途径进化历史的一些重要问题仍然存在。在这里，我们鉴定出了两种能够进行胆固醇生物合成的粘细菌，[具体名称1]和[具体名称2]。与之前已证明能产生胆固醇的粘细菌[具体名称3]以及真核生物中发现的经典途径相比，这两种粘细菌拥有一条在生物合成的顺序和所涉及的酶方面都有所不同的胆固醇生物合成途径。我们表征了一种负责进行C - 24还原的替代细菌还原酶，进一步明确了细菌胆固醇产生与真核生物的差异。最后，我们研究了固醇生物合成蛋白在已培养和未培养的粘球菌门物种中的分布及系统发育关系，为家族水平上的多次获取事件以及水平和垂直转移实例提供了证据。总之，这项工作进一步证明了粘细菌合成真核生物固醇的能力，但在控制固醇合成的生化反应中存在潜在的多样性，这表明了其复杂的进化历史，并完善了我们对粘细菌胆固醇产生与真核生物对应物之间关系的理解。
固醇在真核生物中是必不可少且普遍存在的脂质，但它们在细菌中的重要性却鲜为人知。粘球菌门是一类发育复杂的捕食性细菌，该门中固醇产生为新型固醇生物化学提供了见解，并引发了关于真核生物和细菌域中这一途径进化的讨论。在这里，我们表征了两种粘细菌中的胆固醇生物合成，为不同的途径组织提供了证据，并鉴定出一种负责C - 24还原的独特蛋白质。我们将这些结果与粘球菌门内固醇生物合成的系统基因组分析相结合，揭示了一个以垂直和水平转移为特征的复杂进化历史。这表明粘球菌门中该途径是通过镶嵌式获取的，并突出了粘细菌在固醇向真核生物转移中可能具有的复杂作用。
