{"doi":"10.1101/2023.10.17.562681","title":"A purine salvage bottleneck leads to bacterial adenine cross-feeding","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Diverse ecosystems host microbial relationships that are stabilized by nutrient cross-feeding. Cross-feeding can involve metabolites that should hold value for the producer. Externalization of such communally valuable metabolites is often unexpected and difficult to predict. Previously, we fortuitously discovered purine externalization by\n                  <jats:italic>Rhodopseudomonas palustris</jats:italic>\n                  by its ability to rescue growth of an\n                  <jats:italic>Escherichia coli</jats:italic>\n                  purine auxotroph. Here we found that an\n                  <jats:italic>E. coli</jats:italic>\n                  purine auxotroph can stably coexist with\n                  <jats:italic>R. palustris</jats:italic>\n                  due to purine cross-feeding. We identified the cross-fed purine as adenine. Adenine was externalized by\n                  <jats:italic>R. palustris</jats:italic>\n                  under diverse growth conditions. Computational models suggested that adenine externalization occurs via passive diffusion across the cytoplasmic membrane. RNAseq analysis led us to hypothesize that accumulation and externalization of adenine stems from an adenine salvage bottleneck at the enzyme encoded by\n                  <jats:italic>apt</jats:italic>\n                  . Ectopic expression of\n                  <jats:italic>apt</jats:italic>\n                  eliminated adenine externalization, supporting our hypothesis. A comparison of 49\n                  <jats:italic>R. palustris</jats:italic>\n                  strains suggested that purine externalization is relatively common, with 15 of the strains exhibiting the trait. Purine externalization was correlated with the genomic orientation of\n                  <jats:italic>apt</jats:italic>\n                  orientation, but\n                  <jats:italic>apt</jats:italic>\n                  orientation alone could not explain adenine externalization in some strains. Our results provide a mechanistic understanding of how a communally valuable metabolite can participate in cross-feeding. Our findings also highlight the challenge in identifying genetic signatures for metabolite externalization.\n                </jats:p>","journal":null,"year":null,"id":657543,"datarank":0.23895337014040222,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.031009215972418604,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.031009215972418604,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":588421,"name":"Nicholas W. Haas","orcid":null,"position":1,"is_corresponding":false},{"id":587941,"name":"Robert Pepin","orcid":"0000-0002-1828-1598","position":2,"is_corresponding":false},{"id":821331,"name":"Megan G. Behringer","orcid":"0000-0001-7036-6014","position":3,"is_corresponding":false},{"id":769030,"name":"Yasuhiro Oda","orcid":"0000-0003-2554-7371","position":4,"is_corresponding":false},{"id":1235294,"name":"Breah LaSarre","orcid":"0000-0002-2723-8217","position":5,"is_corresponding":false},{"id":769032,"name":"Caroline S. Harwood","orcid":"0000-0003-4450-5177","position":6,"is_corresponding":false},{"id":825722,"name":"James B. McKinlay","orcid":"0000-0003-2401-6229","position":7,"is_corresponding":false},{"id":1337233,"name":"Ying-Chih Chuang","orcid":"0000-0002-3626-6631","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A purine salvage bottleneck leads to bacterial adenine cross-feeding","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Diverse ecosystems host microbial relationships that are stabilized by nutrient cross-feeding. Cross-feeding can involve metabolites that should hold value for the producer. Externalization of such communally valuable metabolites is often unexpected and difficult to predict. Previously, we fortuitously discovered purine externalization by\n                  <jats:italic>Rhodopseudomonas palustris</jats:italic>\n                  by its ability to rescue growth of an\n                  <jats:italic>Escherichia coli</jats:italic>\n                  purine auxotroph. Here we found that an\n                  <jats:italic>E. coli</jats:italic>\n                  purine auxotroph can stably coexist with\n                  <jats:italic>R. palustris</jats:italic>\n                  due to purine cross-feeding. We identified the cross-fed purine as adenine. Adenine was externalized by\n                  <jats:italic>R. palustris</jats:italic>\n                  under diverse growth conditions. Computational models suggested that adenine externalization occurs via passive diffusion across the cytoplasmic membrane. RNAseq analysis led us to hypothesize that accumulation and externalization of adenine stems from an adenine salvage bottleneck at the enzyme encoded by\n                  <jats:italic>apt</jats:italic>\n                  . Ectopic expression of\n                  <jats:italic>apt</jats:italic>\n                  eliminated adenine externalization, supporting our hypothesis. A comparison of 49\n                  <jats:italic>R. palustris</jats:italic>\n                  strains suggested that purine externalization is relatively common, with 15 of the strains exhibiting the trait. Purine externalization was correlated with the genomic orientation of\n                  <jats:italic>apt</jats:italic>\n                  orientation, but\n                  <jats:italic>apt</jats:italic>\n                  orientation alone could not explain adenine externalization in some strains. Our results provide a mechanistic understanding of how a communally valuable metabolite can participate in cross-feeding. Our findings also highlight the challenge in identifying genetic signatures for metabolite externalization.\n                </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37904951","pmcid":null,"openalex_id":"https://openalex.org/W4387730878","authors":[],"funders":[{"funder_name":"National Science Foundation","grant_id":"1749489","title":"CAREER:  The impact of spatial-positioning mechanisms on the metabolic interactions and emergent properties of synthetic bacterial communities"},{"funder_name":"National Institutes of Health","grant_id":"5R35GM150625-02","title":"Using Experimental Evolution to Evaluate Environmental Effects on Microbial Mutation and Adaptation"},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM150625","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/10/17/2023.10.17.562681.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2023/10/17/2023.10.17.562681.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2023.10.17.562681","host_type":"publisher"},{"url":"https://doi.org/10.1101/2023.10.17.562681","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37904951","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10614841","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10614841/pdf/nihpp-2023.10.17.562681v1.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.1101/2023.10.17.562681","host_type":""}],"fields_of_study":["Bacterial Genetics and Biotechnology","Microbial Community Ecology and Physiology","Bacteriophages and microbial interactions","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Purine","Externalization","Biology","Metabolite","Rhodopseudomonas palustris","Biochemistry","Enzyme","Genetics","Bacteria","Psychology","Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T01:30:36.784229Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}