LucaPCycle: Illuminating microbial phosphorus cycling in deep-sea cold seep sediments using protein language models

Chuwen Zhang, Yong He, Jieni Wang, Tengkai Chen, Federico Baltar, Minjie Hu, Jing Liao, Xi Xiao, Zhao-Rong Li () and Xiyang Dong ()
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Chuwen Zhang: Ministry of Natural Resources
Yong He: Alibaba Group
Jieni Wang: Ministry of Natural Resources
Tengkai Chen: Ministry of Natural Resources
Federico Baltar: Shanghai Ocean University
Minjie Hu: Fujian Normal University
Jing Liao: Ministry of Natural Resources
Xi Xiao: China Geological Survey
Zhao-Rong Li: Alibaba Group
Xiyang Dong: Ministry of Natural Resources

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Phosphorus is essential for life and critically influences marine productivity. Despite geochemical evidence of active phosphorus cycling in deep-sea cold seeps, the microbial processes involved remain poorly understood. Traditional sequence-based searches often fail to detect proteins with remote homology. To address this, we developed a deep learning model, LucaPCycle, integrating raw sequences and contextual embeddings based on the protein language model ESM2-3B. LucaPCycle identified 5241 phosphorus-cycling protein families from global cold seep gene and genome catalogs, substantially enhancing our understanding of their diversity, ecology, and function. Among previously unannotated sequences, we discovered three alkaline phosphatase families that feature unique domain organizations and preserved enzymatic capabilities. These results highlight previously overlooked ecological importance of phosphorus cycling within cold seeps, corroborated by data from porewater geochemistry, metatranscriptomics, and metabolomics. We revealed a previously unrecognized diversity of archaea, including Asgardarchaeota, anaerobic methanotrophic archaea and Thermoproteota, which contribute to organic phosphorus mineralization and inorganic phosphorus solubilization through various mechanisms. Additionally, auxiliary metabolic genes of cold seep viruses primarily encode the PhoR-PhoB regulatory system and PhnCDE transporter, potentially enhancing their hosts’ phosphorus utilization. Overall, LucaPCycle are capable of accessing previously ‘hidden’ sequence spaces for microbial phosphorus cycling and can be applied to various ecosystems.

Date: 2025
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DOI: 10.1038/s41467-025-60142-4

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