Branched-chain amino acid specialization drove diversification within Calditenuaceae (Caldarchaeia) and enables their cultivation

Many thermophiles that are abundant in high-temperature geothermal systems have never been cultivated and are poorly understood, including deeply branching members of the archaeal phylum Thermoproteota. Here, we describe the genome-guided cultivation of one such organism, Calditenuis ramacidaminiphagus, and show that it has evolved a heterotrophic metabolism focused on branched-chain amino acids (BCAAs). Initially, fluorescence in situ hybridization and nanoscale secondary ion mass spectrometry (FISH-nanoSIMS) showed that Cal. ramacidaminiphagus assimilated amino acids rapidly in casamino acid-amended enrichment cultures. Metagenome and metaproteome analyses showed a high abundance and expression of BCAA transporter genes, suggesting a BCAA-focused metabolism. This inference was supported by the subsequent enrichment of Cal. ramacidaminiphagus in BCAA-fed cultures, reaching 2.66×10<sup>6</sup> cells/mL and 48.7% of the community, whereas it was outcompeted when polar amino acids were included. Metabolic reconstruction and metaproteomics suggest that BCAAs are channeled into the mevalonate pathway for lipid biosynthesis and fuel ATP production through the TCA cycle coupled with aerobic respiration and through production of branched-chain organic acids by overflow metabolism. Ancestral state reconstructions and phylogenetic analyses of 62 Caldarchaeales genomes revealed multiple horizontal transfers of BCAA transporters to the ancestor of the genus Calditenuis. Our study highlights the crucial role of BCAAs in the early evolution and niche of this genus, and suggests a high degree of resource partitioning even within low-diversity thermophilic communities.

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Journal
Nature Communications
Published
2026-02-04
DOI
https://doi.org/10.1038/s41467-026-68859-6
Primary Topic
Genomics and Phylogenetic Studies
Type
article
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article

Branched-chain amino acid specialization drove diversification within Calditenuaceae (Caldarchaeia) and enables their cultivation

Dengxun Lai, Damon Mosier, Zheng‐Shuang Hua, Brian P. Hedlund et al.
Nature Communications
Genomics and Phylogenetic Studies
article

Branched-chain amino acid specialization drove diversification within Calditenuaceae (Caldarchaeia) and enables their cultivation

Dengxun Lai, Damon Mosier, Zheng‐Shuang Hua, Brian P. Hedlund, Daniel R. Colman, Peter Weber, Jeremy A. Dodsworth, Xavier Mayali, Marike Palmer, W. Q. Li, Cale O. Seymour, Eric S. Boyd, Juliet Johnston, Jonathan K. Covington, Takuro Nunoura, Walter Saldivar, Ranjani Murali, Jennifer Pett-Ridge, Jian-Yu Jiao, Lan Liu
article en

Abstract

Many thermophiles that are abundant in high-temperature geothermal systems have never been cultivated and are poorly understood, including deeply branching members of the archaeal phylum Thermoproteota. Here, we describe the genome-guided cultivation of one such organism, Calditenuis ramacidaminiphagus, and show that it has evolved a heterotrophic metabolism focused on branched-chain amino acids (BCAAs). Initially, fluorescence in situ hybridization and nanoscale secondary ion mass spectrometry (FISH-nanoSIMS) showed that Cal. ramacidaminiphagus assimilated amino acids rapidly in casamino acid-amended enrichment cultures. Metagenome and metaproteome analyses showed a high abundance and expression of BCAA transporter genes, suggesting a BCAA-focused metabolism. This inference was supported by the subsequent enrichment of Cal. ramacidaminiphagus in BCAA-fed cultures, reaching 2.66×10<sup>6</sup> cells/mL and 48.7% of the community, whereas it was outcompeted when polar amino acids were included. Metabolic reconstruction and metaproteomics suggest that BCAAs are channeled into the mevalonate pathway for lipid biosynthesis and fuel ATP production through the TCA cycle coupled with aerobic respiration and through production of branched-chain organic acids by overflow metabolism. Ancestral state reconstructions and phylogenetic analyses of 62 Caldarchaeales genomes revealed multiple horizontal transfers of BCAA transporters to the ancestor of the genus Calditenuis. Our study highlights the crucial role of BCAAs in the early evolution and niche of this genus, and suggests a high degree of resource partitioning even within low-diversity thermophilic communities.

Nature CommunicationsVol. 17(1)
University of Science and Technology of China (CN), Lawrence Livermore National Laboratory (US), Japan Agency for Marine-Earth Science and Technology (JP), University of Nevada, Las Vegas (US), Sun Yat-sen University (CN), University of Calgary (CA), Aarhus University (DK), Montana State University (US), Institute of Ecology and Geography (MD), Xinjiang Institute of Ecology and Geography (CN), Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (CN), California State University, San Bernardino (US), University of Manitoba (CA)
National Science Foundation, National Aeronautics and Space Administration, National Natural Science Foundation of China, Nuclear Safety and Security Commission, Novo Nordisk, Novo Nordisk Fonden, National Park Service, Lawrence Livermore National Laboratory
Openalex Percentile: Top 68%
Genomics and Phylogenetic Studies
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