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通过筛选海洋来源细菌单培养物和共培养物中的天然产物谱发现肽类铁载体降解作用

Discovery of Peptidic Siderophore Degradation by Screening Natural Product Profiles in Marine-Derived Bacterial Mono- and Cocultures.

作者信息

Monge-Loría Mónica, Zhong Weimao, Abrahamse Nadine H, Hartter Stephen, Garg Neha

机构信息

School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia 30332, United States.

Georgia Aquarium, 225 Baker St. NW, Atlanta, Georgia 30313, United States.

出版信息

Biochemistry. 2025 Feb 4;64(3):634-654. doi: 10.1021/acs.biochem.4c00706. Epub 2025 Jan 14.

Abstract

Coral reefs are hotspots of marine biodiversity, which results in the synthesis of a wide variety of compounds with unique molecular scaffolds, and bioactivities, rendering reefs an ecosystem of interest. The chemodiversity stems from the intricate relationships between inhabitants of the reef, as the chemistry produced partakes in intra- and interspecies communication, settlement, nutrient acquisition, and defense. However, the coral reefs are declining at an unprecedented rate due to climate change, pollution, and increased incidence of pathogenic diseases. Among pathogens, spp. bacteria are key players resulting in high mortality. Thus, alternative strategies such as application of beneficial bacteria isolated from disease-resilient species are being explored to lower the burden of pathogenic species. Here, we apply coculturing of a coral-derived pathogenic species of and beneficial bacteria and leverage recent advancements in untargeted metabolomics to discover engineerable beneficial traits. By chasing chemical change in coculture, we report spp.-mediated degradation of amphibactins, produced by spp. bacteria to sequester iron. Additional biochemical experiments revealed that the degradation occurs in the peptide backbone and requires the enzyme fraction of . A reduction in iron affinity is expected due to the loss of one Fe(III) binding moiety. Therefore, we hypothesize that this degradation shapes community behaviors as it pertains to iron acquisition, a limiting nutrient in the marine environment, and survival. Furthermore, sp. bacteria suppressed natural product synthesis by beneficial bacteria. Understanding biochemical mechanisms behind these interactions will enable engineering probiotic bacteria capable of lowering pathogenic burdens during heat waves and incidence of disease.

摘要

珊瑚礁是海洋生物多样性的热点地区,这导致合成了各种具有独特分子支架和生物活性的化合物,使珊瑚礁成为一个令人感兴趣的生态系统。化学多样性源于珊瑚礁生物之间复杂的关系,因为所产生的化学物质参与了种内和种间的交流、定居、养分获取和防御。然而,由于气候变化、污染和致病疾病发病率的增加,珊瑚礁正以前所未有的速度衰退。在病原体中, 属细菌是导致高死亡率的关键因素。因此,人们正在探索诸如应用从抗病物种中分离出的有益细菌等替代策略,以减轻致病物种的负担。在这里,我们将一种源自珊瑚的致病 属物种与有益细菌进行共培养,并利用非靶向代谢组学的最新进展来发现可工程化的有益特性。通过追踪共培养中的化学变化,我们报告了 属介导的对两栖菌素的降解,两栖菌素由 属细菌产生以螯合铁。额外的生化实验表明,降解发生在肽主链上,并且需要 的酶组分。由于失去了一个Fe(III)结合部分,预计铁亲和力会降低。因此,我们假设这种降解塑造了与铁获取(海洋环境中的一种限制性营养素)和生存相关的群落行为。此外, 属细菌抑制了有益细菌的天然产物合成。了解这些相互作用背后的生化机制将有助于设计出能够在热浪和疾病发生期间降低致病负担的益生菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b77a/11800396/9c0e3d2b6926/bi4c00706_0001.jpg

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