{"doi":"10.1101/2020.05.27.120295","title":"<i>Burkholderia thailandensis</i> methylated hydroxy-alkylquinolines: biosynthesis and antimicrobial activity in co-cultures","abstract":"ABSTRACT The bacterium Burkholderia thailandensis produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology of this soil-dwelling bacterium. In liquid co-culture experiments, B. thailandensis secretes an antimicrobial that nearly eliminates another soil bacterium, Bacillus subtilis . To identify the antimicrobial, we used a transposon mutagenesis approach. This screen identified antimicrobial-defective mutants with insertions in the hmqA, hmqC and hmqF genes involved in biosynthesis of a family of 2-alkyl-4(1 H )-quinolones called 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs), which are closely related to the Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs). Insertions also occurred in the previously uncharacterized gene BTH_II1576. Results confirm that BTH_II1576 is involved in generating N- oxide derivatives of HMAQs (HMAQ-NO) in B. thailandensis and that HMAQ-NOs are sufficient to eliminate B. subtilis in co-cultures. Moreover, synthetic HMAQ-NO is ∼50-fold more active than HMAQ. Both the methyl group and the length of the carbon side chain account for high activity of HMAQ-NO against B. subtilis . The results provide new information on the biosynthesis and activities of HMAQs and reveal new insight into how these molecules might be important for the ecology of B. thailandensis . IMPORTANCE The soil bacterium Burkholderia thailandensis produces 2-alkyl-4(1 H )-quinolones, mostly methylated 4-hydroxy - alkenylquinolines, a family of relatively unstudied metabolites similar to molecules also synthesized by Pseudomonas aeruginosa . Several of the methylated 4-hydroxy-alkenylquinolines have antimicrobial activity against other species. We show that N- oxidated methyl-alkenylquinolines are particularly antimicrobial and sufficient to kill Bacillus subtilis in co-cultures. We confirmed their biosynthesis requires the previously unstudied protein HmqL. These results provide new information about the biology of 2-alkyl-4(1 H )-quinolones, particularly the methylated 4-hydroxy - alkenylquinolines, which are unique to B. thailandensis . This study also has importance for understanding B. thailandensis secondary metabolites and has implications for potential therapeutic development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126743,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":368139,"name":"Charlotte D. Majerczyk","orcid":null,"position":1,"is_corresponding":false},{"id":344065,"name":"Stephanie L. Moon","orcid":"0000-0002-4989-0150","position":2,"is_corresponding":false},{"id":575244,"name":"Natalie A. Epplera","orcid":null,"position":3,"is_corresponding":false},{"id":367204,"name":"Sierra Smith","orcid":"0000-0002-0120-8765","position":4,"is_corresponding":false},{"id":368141,"name":"Emily Tuma","orcid":null,"position":5,"is_corresponding":false},{"id":367205,"name":"Marie‐Christine Groleau","orcid":"0000-0003-4810-1030","position":6,"is_corresponding":false},{"id":282326,"name":"Kyle L. Asfahl","orcid":"0000-0001-5626-3529","position":7,"is_corresponding":false},{"id":367206,"name":"Nicole E. Smalley","orcid":"0000-0003-3863-4335","position":8,"is_corresponding":false},{"id":277190,"name":"Hillary S. Hayden","orcid":"0000-0001-7372-9853","position":9,"is_corresponding":false},{"id":367207,"name":"Marianne Piochon","orcid":"0000-0003-4082-8120","position":10,"is_corresponding":false},{"id":368142,"name":"Patrick N. Ball","orcid":null,"position":11,"is_corresponding":false},{"id":282330,"name":"Ajai A. Dandekar","orcid":"0000-0002-2992-6523","position":12,"is_corresponding":false},{"id":367208,"name":"Charles Gauthier","orcid":"0000-0002-2475-2050","position":13,"is_corresponding":false},{"id":367209,"name":"Éric Déziel","orcid":"0000-0002-4609-0115","position":14,"is_corresponding":false},{"id":367210,"name":"Josephine R. Chandler","orcid":"0000-0001-8944-9813","position":15,"is_corresponding":false},{"id":367203,"name":"Jennifer R. Klaus","orcid":"0000-0001-9821-1487","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}