{"doi":"10.1128/jb.02546-14","title":"Biosynthesis of Cell Envelope-Associated Phenolic Glycolipids in Mycobacterium marinum","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Phenolic glycolipids (PGLs) are polyketide synthase-derived glycolipids unique to pathogenic mycobacteria. PGLs are found in several clinically relevant species, including various\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis</jats:named-content>\n            strains,\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium leprae</jats:named-content>\n            , and several nontuberculous mycobacterial pathogens, such as\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. marinum</jats:named-content>\n            . Multiple lines of investigation implicate PGLs in virulence, thus underscoring the relevance of a deep understanding of PGL biosynthesis. We report mutational and biochemical studies that interrogate the mechanism by which PGL biosynthetic intermediates (\n            <jats:italic>p</jats:italic>\n            -hydroxyphenylalkanoates) synthesized by the iterative polyketide synthase Pks15/1 are transferred to the noniterative polyketide synthase PpsA for acyl chain extension in\n            <jats:named-content xmlns:xlink=\"http://www.w3.org/1999/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. marinum</jats:named-content>\n            . Our findings support a model in which the transfer of the intermediates is dependent on a\n            <jats:italic>p</jats:italic>\n            -hydroxyphenylalkanoyl-AMP ligase (FadD29) acting as an intermediary between the iterative and the noniterative synthase systems. Our results also establish the\n            <jats:italic>p</jats:italic>\n            -hydroxyphenylalkanoate extension ability of PpsA, the first-acting enzyme of a multisubunit noniterative polyketide synthase system. Notably, this noniterative system is also loaded with fatty acids by a specific fatty acyl-AMP ligase (FadD26) for biosynthesis of phthiocerol dimycocerosates (PDIMs), which are nonglycosylated lipids structurally related to PGLs. To our knowledge, the partially overlapping PGL and PDIM biosynthetic pathways provide the first example of two distinct, pathway-dedicated acyl-AMP ligases loading the same type I polyketide synthase system with two alternate starter units to produce two structurally different families of metabolites. The studies reported here advance our understanding of the biosynthesis of an important group of mycobacterial glycolipids.\n          </jats:p>","journal":"Journal of Bacteriology","year":2015,"id":37379,"datarank":0.9764533731426197,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.5127970051388723,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.5127970051388723,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":19,"citers_with_citation_signal":17,"citers_with_endowment":17,"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":187437,"name":"Sivagami Sundaram Chavadi","orcid":null,"position":1,"is_corresponding":false},{"id":187438,"name":"Uthamaphani R. Edupuganti","orcid":null,"position":2,"is_corresponding":false},{"id":187439,"name":"Poornima Mohandas","orcid":null,"position":3,"is_corresponding":false},{"id":187440,"name":"Catherine Chan","orcid":null,"position":4,"is_corresponding":false},{"id":187441,"name":"Julie Zeng","orcid":null,"position":5,"is_corresponding":false},{"id":187442,"name":"Mykhailo Kopylov","orcid":null,"position":6,"is_corresponding":false},{"id":187443,"name":"Nicholas G. Angelo","orcid":null,"position":7,"is_corresponding":false},{"id":187444,"name":"J. David Warren","orcid":null,"position":8,"is_corresponding":false},{"id":187445,"name":"Clifford E. Soll","orcid":null,"position":9,"is_corresponding":false},{"id":187446,"name":"Luis E. N. Quadri","orcid":null,"position":10,"is_corresponding":false},{"id":187436,"name":"Olivia Vergnolle","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25561717","pmcid":"PMC4336343","openalex_id":"https://openalex.org/W2025799059","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R15AI10588","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R15 AI105884","title":null}],"total_grants":2,"fwci":1.7363,"citation_percentile":0.84624816,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":4},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":2},{"year":2020,"count":5},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2025,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jb.asm.org/content/jb/197/6/1040.full.pdf","host_type":"journal"},{"url":"https://doi.org/10.1128/jb.02546-14","host_type":"GREEN"},{"url":"https://jb.asm.org/content/jb/197/6/1040.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JB.02546-14","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25561717","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4336343","host_type":"repository"}],"fields_of_study":["Mycobacterium research and diagnosis","Microbial Natural Products and Biosynthesis","Tuberculosis Research and Epidemiology","Medicine","Biology","Chemistry","Acyl Carrier Protein","Bacterial Proteins","Cell Membrane","Gene Expression Regulation, Bacterial","Glycolipids","Molecular Structure","Mutation","Mycobacterium marinum","Phenols","Protein Structure, Tertiary","Species Specificity"],"mesh_terms":["Acyl Carrier Protein","Bacterial Proteins","Cell Membrane","Glycolipids","Mutation","Phenols","Species Specificity","Molecular Structure","Gene Expression Regulation, Bacterial","Protein Structure, Tertiary","Mycobacterium marinum"],"keywords":["Polyketide synthase","Biology","Mycobacterium marinum","Polyketide","Biochemistry","Biosynthesis","Glycolipid","DNA ligase","Acyl carrier protein","ATP synthase","Mycobacterium tuberculosis","Mycobacterium","Enzyme","Microbiology","Bacteria","Genetics","Tuberculosis"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T19:19:55.343347Z","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":[]}