{"doi":"10.1007/s10295-016-1847-2","title":"Biosynthesis, regulation, and engineering of a linear polyketide tautomycetin: a novel immunosuppressant in <i>Streptomyces</i> sp. CK4412","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Tautomycetin (TMC) is a natural product with a linear structure that includes an ester bond connecting a dialkylmaleic moiety to a type I polyketide chain. Although TMC was originally identified as an antifungal antibiotic in the late 1980s, follow-up studies revealed its novel immunosuppressant activity. Specifically, TMC exhibited a mechanistically unique immunosuppressant activity about 100 times higher than that of cyclosporine A, a widely used immunosuppressant drug. Interestingly, a structurally close relative, tautomycin (TTM), was reported to not possess TMC-like immunosuppressant activity, suggesting that a distinctive polyketide moiety of TMC plays a critical role in immunosuppressant activity. Cloning and engineering of a TMC polyketide biosynthetic gene cluster generated several derivatives showing different biological activities. TMC was also found to be biosynthesized as a linear structure without forming a lactone ring, unlike the most polyketide-based compounds, implying the presence of a unique polyketide thioesterase in the cluster. Although TMC biosynthesis was limited due to its tight regulation by two pathway-specific regulatory genes located in the cluster, its production was significantly stimulated through homologous and heterologous expression of its entire biosynthetic gene cluster using a Streptomyces artificial chromosome vector system. In this mini-review, we summarize recent advances in the biosynthesis, regulation, and pathway engineering of a linear polyketide, TMC, in Streptomyces sp. CK4412.</jats:p>","journal":"Journal of Industrial Microbiology and Biotechnology","year":2017,"id":682483,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1782999,"name":"Hee-Ju Nah","orcid":null,"position":1,"is_corresponding":false},{"id":1783000,"name":"Hye-rim Pyeon","orcid":null,"position":2,"is_corresponding":false},{"id":1783001,"name":"Eung-Soo Kim","orcid":null,"position":3,"is_corresponding":false},{"id":1782998,"name":"Si-Sun Choi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Biosynthesis, regulation, and engineering of a linear polyketide tautomycetin: a novel immunosuppressant in <i>Streptomyces</i> sp. CK4412","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Tautomycetin (TMC) is a natural product with a linear structure that includes an ester bond connecting a dialkylmaleic moiety to a type I polyketide chain. Although TMC was originally identified as an antifungal antibiotic in the late 1980s, follow-up studies revealed its novel immunosuppressant activity. Specifically, TMC exhibited a mechanistically unique immunosuppressant activity about 100 times higher than that of cyclosporine A, a widely used immunosuppressant drug. Interestingly, a structurally close relative, tautomycin (TTM), was reported to not possess TMC-like immunosuppressant activity, suggesting that a distinctive polyketide moiety of TMC plays a critical role in immunosuppressant activity. Cloning and engineering of a TMC polyketide biosynthetic gene cluster generated several derivatives showing different biological activities. TMC was also found to be biosynthesized as a linear structure without forming a lactone ring, unlike the most polyketide-based compounds, implying the presence of a unique polyketide thioesterase in the cluster. Although TMC biosynthesis was limited due to its tight regulation by two pathway-specific regulatory genes located in the cluster, its production was significantly stimulated through homologous and heterologous expression of its entire biosynthetic gene cluster using a Streptomyces artificial chromosome vector system. In this mini-review, we summarize recent advances in the biosynthesis, regulation, and pathway engineering of a linear polyketide, TMC, in Streptomyces sp. CK4412.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27734184","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://www.springer.com/tdm","oa_locations":[{"url":"http://link.springer.com/content/pdf/10.1007/s10295-016-1847-2.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1007/s10295-016-1847-2/fulltext.html","host_type":"publisher"},{"url":"http://academic.oup.com/jimb/article-pdf/44/4-5/555/36747160/jimb0555.pdf","host_type":"publisher"}],"fields_of_study":["Medicine","Biology","Chemistry","Engineering"],"mesh_terms":["Chromosomes, Artificial, Bacterial","Streptomyces","Furans","Lipids","Immunosuppressive Agents","Antifungal Agents","Protein Engineering","Gene Expression Regulation, Bacterial","Genes, Regulator","Multigene Family","Polyketides","Microorganisms, Genetically-Modified"],"keywords":["Biosynthesis","Immunosuppressant","Tautomycetin","Linear Polyketide"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T20:32:53.542069Z","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":[]}