Identification and characterization of a small- molecule metallophore involved in lanthanide metabolism

• 成果类型: Article
• 署名作者: Zytnick, Alexa M.; Gutenthaler-Tietze, Sophie M.; Aron, Allegra T.; Reitz, Zachary L.; Phi, Manh Tri; Good, Nathan M.; Petras, Daniel; Daumann, Lena J.; Martinez-Gomez, Norma Cecilia
• 署名单位: University of California System; University of California Berkeley; University of Munich; Heinrich Heine University Dusseldorf; University of Denver; Wageningen University & Research; University of California System; University of California Santa Barbara; Eberhard Karls University of Tubingen
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8837
• DOI: 10.1073/pnas.2322096121
• 发表日期: 2024-08-06
• 关键词: methylobacterium-extorquens am1; pyrroloquinoline quinone; methanol dehydrogenase; mass-spectrometry; transport; systems; genes; pqqa

摘要

Many bacteria secrete metallophores, low- molecular- weight organic compounds that bind ions with high selectivity and affinity, in order to access essential metals from the environment. Previous work has elucidated the structures and biosynthetic machinery of metallophores specific for iron, zinc, nickel, molybdenum, and copper. No physiologically relevant lanthanide- binding metallophore has been discovered despite the knowledge that lanthanide metals (Ln) have been revealed to be essential cofactors for certain alcohol dehydrogenases across a diverse range of phyla. Here, we report the biosynthetic machinery, the structure, and the physiological relevance of a lanthanophore, methylolanthanin. The structure of methylolanthanin exhibits a unique 4- hydroxybenzoate moiety which has not previously been described in other metallophores. We find that production of methylolanthanin is required for normal levels of Ln accumulation in the methylotrophic bacterium Methylobacterium extorquens AM1, while overexpression of the molecule greatly increases bioaccumulation and adsorption. Our results provide a clearer understanding of how Ln- utilizing bacteria sense, scavenge, and store Ln; essential processes in the environment where Ln are poorly bioavailable. More broadly, the identification of this lanthanophore opens doors for study of how biosynthetic gene clusters are repurposed for additional functions and the complex relationship between metal homeostasis and fitness.