{"doi":"10.1073/pnas.2009306117","title":"Studies of lincosamide formation complete the biosynthetic pathway for lincomycin A","abstract":"Significance Lincomycin A is an antibiotic used clinically in the treatment of Gram-positive bacterial infections. Its biosynthesis has attracted much attention due to its unique sulfur-containing thiooctose core. Despite significant progress in our understanding of lincomycin biosynthesis, the mechanism by which GDP-ᴅ- erythro -α-ᴅ- gluco -octose maturates to GDP-ᴅ-α-ᴅ-lincosamide remains obscure. Herein, the long-sought missing link is established to consist of two epimerizations: a 6,8-dehydration and a transamination reaction catalyzed by four enzymes. Furthermore, unlike other epimerases that function regiospecifically, a single enzyme is found to catalyze epimerization at two different loci. Also, the dehydration is shown to be an α,γ-dehydration catalyzed by two enzymes. This study thus completes the description of the lincomycin biosynthetic pathway and highlights the complex mechanistic subtleties of unusual sugar biosynthesis.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":105727,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":511777,"name":"Chia‐I Lin","orcid":null,"position":1,"is_corresponding":false},{"id":511415,"name":"Jiawei Zhang","orcid":"0000-0003-1765-9349","position":2,"is_corresponding":false},{"id":511416,"name":"Richiro Ushimaru","orcid":"0000-0002-4071-3326","position":3,"is_corresponding":false},{"id":511417,"name":"Eita Sasaki","orcid":"0000-0002-8202-4465","position":4,"is_corresponding":false},{"id":419939,"name":"Hung‐wen Liu","orcid":"0000-0001-8953-4794","position":5,"is_corresponding":false},{"id":419936,"name":"Shao‐An Wang","orcid":"0000-0002-5473-4195","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:12:21.275494Z","pmid":"32958639","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":[]}