{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:33:25Z","timestamp":1772768005391,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0905704 and 2019YFA0905100"],"award-info":[{"award-number":["2019YFA0905704 and 2019YFA0905100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32025001, 82022066, 81741155 and 32000039"],"award-info":[{"award-number":["32025001, 82022066, 81741155 and 32000039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013352","name":"Weihai Science and Technology Development Program","doi-asserted-by":"publisher","award":["2018ZC11"],"award-info":[{"award-number":["2018ZC11"]}],"id":[{"id":"10.13039\/501100013352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2019ZD20"],"award-info":[{"award-number":["ZR2019ZD20"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology (Qingdao)","award":["LMDBKF-2019-01"],"award-info":[{"award-number":["LMDBKF-2019-01"]}]},{"name":"The State Key Laboratory of Bio-organic and Natural Products Chemistry","award":["SKLBNPC18242"],"award-info":[{"award-number":["SKLBNPC18242"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Bafilomycin A1 is the representative compound of the plecomacrolide natural product family. This 16-membered ring plecomacrolide has potent antifungal and vacuolar H+-ATPase inhibitory activities. In our previous work, we identified a bafilomycin biosynthetic gene cluster (baf) from the marine bacterium Streptomyces lohii ATCC BAA-1276, wherein a luxR family regulatory gene orf1 and an afsR family regulatory gene bafG were revealed based on bioinformatics analysis. In this study, the positive regulatory roles of orf1 and bafG for bafilomycin biosynthesis are characterized through gene inactivation and overexpression. Compared to the wild-type S. lohii strain, the knockout of either orf1 or bafG completely abolished the production of bafilomycins. The overexpression of orf1 or bafG led to 1.3- and 0.5-fold increased production of bafilomycins, respectively. A genetically engineered S. lohii strain (SLO-08) with orf1 overexpression and inactivation of the biosynthetic genes orf2 and orf3, solely produced bafilomycin A1 with the titer of 535.1 \u00b1 25.0 mg\/L in an optimized fermentation medium in shaking flasks. This recombinant strain holds considerable application potential in large-scale production of bafilomycin A1 for new drug development.<\/jats:p>","DOI":"10.3390\/md19010029","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:36:11Z","timestamp":1610364971000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Engineering Bafilomycin High-Producers by Manipulating Regulatory and Biosynthetic Genes in the Marine Bacterium Streptomyces lohii"],"prefix":"10.3390","volume":"19","author":[{"given":"Zhong","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"},{"name":"Shandong Provincial Key Laboratory of Synthetic Biology, CAS Key Laboratory of Biofuels at Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China"},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2245-7100","authenticated-orcid":false,"given":"Lei","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingwang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"},{"name":"Shandong Provincial Key Laboratory of Synthetic Biology, CAS Key Laboratory of Biofuels at Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China"},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhua","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-870X","authenticated-orcid":false,"given":"Shengying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"},{"name":"Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.7164\/antibiotics.37.110","article-title":"Metabolic products of microorganisms. 224. Bafilomycins, a new group of macrolide antibiotics. Production, isolation, chemical structure and biological activity","volume":"37","author":"Werner","year":"1984","journal-title":"J. Antibiot."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.7164\/antibiotics.37.1333","article-title":"Isolation and characterization of concanamycins A, B and C","volume":"37","author":"Kinashi","year":"1984","journal-title":"J. Antibiot."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.7164\/antibiotics.38.1449","article-title":"PD 118,576: A new antitumor macrolide antibiotic","volume":"38","author":"Wilton","year":"1985","journal-title":"J. Antibiot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1073\/pnas.85.21.7972","article-title":"Bafilomycins: A class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells","volume":"85","author":"Bowman","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1016\/S0040-4039(00)88394-X","article-title":"The structure of the bafilomycins, a new group of macrolide antibiotics","volume":"24","author":"Werner","year":"1983","journal-title":"Tetrahedron Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1016\/j.tetlet.2016.09.066","article-title":"Bafilomycin M, a new cytotoxic bafilomycin produced by a Streptomyces sp. isolated from a marine sponge Theonella sp.","volume":"57","author":"Chen","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"151874","DOI":"10.1016\/j.tetlet.2020.151874","article-title":"Cytotoxic bafilomycin analogues 6\/5\/5 with tricyclic ring system from a marine-derived Streptomyces sp.","volume":"61","author":"Li","year":"2020","journal-title":"Tetrahedron Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/ja.2017.33","article-title":"Characterization of bafilomycin biosynthesis in Kitasatospora setae KM-6054 and comparative analysis of gene clusters in Actinomycetales microorganisms","volume":"70","author":"Nara","year":"2017","journal-title":"J. Antibiot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7095","DOI":"10.1074\/jbc.M116.751255","article-title":"Complete elucidation of the late steps of bafilomycin biosynthesis in Streptomyces lohii","volume":"292","author":"Li","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1021\/acschembio.5b00801","article-title":"Leucanicidin and endophenasides result from methyl-rhamnosylation by the same tailoring enzymes in Kitasatospora sp. MBT66","volume":"11","author":"Wu","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7007","DOI":"10.1038\/ncomms8007","article-title":"Autophagosome\u2013lysosome fusion is independent of V-ATPase-mediated acidification","volume":"6","author":"Mauvezin","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1128\/AAC.44.3.739-746.2000","article-title":"Synergistic antifungal activities of bafilomycin A1, fluconazole, and the pneumocandin MK-0991\/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans","volume":"44","author":"Cruz","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","first-page":"643","article-title":"Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal effect and induces endoplasmic reticulum stress in U266 myeloma cells: Crosstalk among proteasome, autophagy-lysosome and ER stress","volume":"38","author":"Kawaguchi","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s13277-015-3842-z","article-title":"Inhibition of autophagy by bafilomycin A1 promotes chemosensitivity of gastric cancer cells","volume":"37","author":"Li","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.7150\/ijbs.45498","article-title":"Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19","volume":"16","author":"Yang","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1242\/jeb.200.1.1","article-title":"Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases","volume":"200","author":"Altendorf","year":"1997","journal-title":"J. Exp. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1021\/jm9707838","article-title":"Synthesis and structure-activity relationships of bafilomycin A1 derivatives as inhibitors of vacuolar H+-ATPase","volume":"41","author":"Gagliardi","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/anie.200804645","article-title":"Total synthesis of bafilomycin A1","volume":"48","author":"Kleinbeck","year":"2009","journal-title":"Angew. Chem. Int. Edit."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.1021\/ja017885e","article-title":"Total synthesis of (-)-bafilomycin A1","volume":"124","author":"Scheidt","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/cbic.201200743","article-title":"Characterization of the bafilomycin biosynthetic gene cluster from Streptomyces lohii","volume":"14","author":"Zhang","year":"2013","journal-title":"ChemBioChem"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2191-0855-3-24","article-title":"Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608","volume":"3","author":"Hwang","year":"2013","journal-title":"AMB Express"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12275-015-4340-0","article-title":"Analysis of a draft genome sequence of Kitasatospora cheerisanensis KCTC 2395 producing bafilomycin antibiotics","volume":"53","author":"Hwang","year":"2015","journal-title":"J. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jbiotec.2017.09.018","article-title":"The complete genome sequence of Streptomyces albolongus YIM 101047, the producer of novel bafilomycins and odoriferous sesquiterpenoids","volume":"262","author":"Yin","year":"2017","journal-title":"J. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1007\/s00253-017-8136-5","article-title":"Comparative proteomic and metabolomic analysis of Streptomyces tsukubaensis reveals the metabolic mechanism of FK506 overproduction by feeding soybean oil","volume":"101","author":"Wang","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0022-2836(83)80284-8","article-title":"Studies on transformation of Escherichia coli with plasmids","volume":"166","author":"Hanahan","year":"1983","journal-title":"J. Mol. Biol."},{"key":"ref_26","unstructured":"Kieser, T. (2000). Practical Streptomyces Genetics, John Innes Foundation."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0378-1119(92)90627-2","article-title":"Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp.","volume":"116","author":"Bierman","year":"1992","journal-title":"Gene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1073\/pnas.0337542100","article-title":"PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin","volume":"100","author":"Gust","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1007\/s00253-014-6369-0","article-title":"An efficient blue-white screening based gene inactivation system for Streptomyces","volume":"99","author":"Li","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_30","first-page":"406","article-title":"The neighbor-joining method: A new method for reconstructing phylogenetic trees","volume":"4","author":"Saitou","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jmb.2007.02.096","article-title":"AfsR recruits RNA polymerase to the afsS promoter: A model for transcriptional activation by SARPs","volume":"369","author":"Tanaka","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12275-007-0233-1","article-title":"The use of the rare UUA codon to define \u201cexpression space\u201d for genes involved in secondary metabolism, development and environmental adaptation in Streptomyces","volume":"46","author":"Chater","year":"2008","journal-title":"J. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1073\/pnas.88.6.2461","article-title":"TTA codons in some genes prevent their expression in a class of developmental, antibiotic-negative, Streptomyces mutants","volume":"88","author":"Leskiw","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1073\/pnas.86.15.5688","article-title":"Identification of the operator of the lux regulon from the Vibrio fischeri strain ATCC 7744","volume":"86","author":"Devine","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1006\/jmbi.2001.4443","article-title":"Crystal structure of GerE, the ultimate transcriptional regulator of spore formation in Bacillus subtilis","volume":"306","author":"Ducros","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1128\/jb.173.9.3000-3009.1991","article-title":"Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression","volume":"173","author":"Gambello","year":"1991","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1128\/jb.170.4.1589-1597.1988","article-title":"Structure of genes narL and narX of the nar (nitrate reductase) locus in Escherichia coli K-12","volume":"170","author":"Stewart","year":"1988","journal-title":"J. Bacteriol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0076-6879(90)83009-X","article-title":"Finding protein similarities with nucleotide sequence databases","volume":"183","author":"Henikoff","year":"1989","journal-title":"Methods Enzymol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1128\/jb.176.2.269-275.1994","article-title":"Quorum sensing in bacteria: The LuxR-LuxI family of cell density-responsive transcriptional regulators","volume":"176","author":"Fuqua","year":"1994","journal-title":"J. Bacteriol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/BF02932090","article-title":"Multiple regulatory genes in the salinomycin biosynthetic gene cluster of Streptomyces albus CCM 4719","volume":"52","author":"Timko","year":"2007","journal-title":"Folia Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9150","DOI":"10.1074\/jbc.M110.182428","article-title":"Molecular control of polyene macrolide biosynthesis: Direct binding of the regulator PimM to eight promoters of pimaricin genes and identification of binding boxes","volume":"286","author":"Vicente","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1099\/mic.0.000033","article-title":"Production of the antibiotic FR-008\/Candicidin in Streptomyces sp. FR-008 is coregulated by two regulators, FscRI and FscRIV, from different transcription factor families","volume":"161","author":"Zhang","year":"2015","journal-title":"Microbiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11115","DOI":"10.1073\/pnas.88.24.11115","article-title":"The C-terminal region of the Vibrio fischeri LuxR protein contains an inducer-independent lux gene activating domain","volume":"88","author":"Choi","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/bab.1443","article-title":"The effect of surfactant on fermentation of kitasamycin in Streptomyces kitasatoensis","volume":"63","author":"Zheng","year":"2016","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"376","DOI":"10.7164\/antibiotics.36.376","article-title":"Elucidation of structure of novel macrolide antibiotics produced by mutant strains of Streptomyces fradiae","volume":"36","author":"Kirst","year":"1983","journal-title":"J. Antibiot."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0378-1119(90)90412-K","article-title":"Primary structure of AfsR, a global regulatory protein for secondary metabolite formation in Streptomyces coelicolor A3 (2)","volume":"95","author":"Horinouchi","year":"1990","journal-title":"Gene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1007\/s10295-003-0063-z","article-title":"AfsR as an integrator of signals that are sensed by multiple serine\/threonine kinases in Streptomyces coelicolor A3 (2)","volume":"30","author":"Horinouchi","year":"2003","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4014\/jmb.0803.223","article-title":"Identification and functional characterization of an afsR homolog regulatory gene from Streptomyces venezuelae ATCC 15439","volume":"19","author":"Maharjan","year":"2009","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1099\/mic.0.047977-0","article-title":"The plant pathogen Streptomyces scabies 87-22 has a functional pyochelin biosynthetic pathway that is regulated by TetR-and AfsR-family proteins","volume":"157","author":"Seipke","year":"2011","journal-title":"Microbiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"672","DOI":"10.4014\/jmb.1409.09091","article-title":"Overexpression of afsR and optimization of metal chloride to improve lomofungin production in Streptomyces lomondensis S015","volume":"25","author":"Wang","year":"2015","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1128\/JB.183.11.3468-3475.2001","article-title":"Characterization and analysis of the PikD regulatory factor in the pikromycin biosynthetic pathway of Streptomyces venezuelae","volume":"183","author":"Wilson","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1099\/mic.0.2008\/018903-0","article-title":"Identification of TmcN as a pathway-specific positive regulator of tautomycetin biosynthesis in Streptomyces sp. CK4412","volume":"154","author":"Hur","year":"2008","journal-title":"Microbiology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1128\/JB.00129-07","article-title":"Roles of rapH and rapG in positive regulation of rapamycin biosynthesis in Streptomyces hygroscopicus","volume":"189","author":"Coates","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1007\/s00253-015-7142-8","article-title":"Characterization of a gamma-butyrolactone synthetase gene homologue (stcA) involved in bafilomycin production and aerial mycelium formation in Streptomyces sp. SBI034","volume":"100","author":"Intra","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8015","DOI":"10.1128\/AEM.02355-12","article-title":"Pleiotropic control of secondary metabolism and morphological development by KsbC, a butyrolactone autoregulator receptor homologue in Kitasatospora setae","volume":"78","author":"Aroonsri","year":"2012","journal-title":"Appl. Environ. Microb."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1128\/JB.186.11.3423-3430.2004","article-title":"Cloning and functional analysis by gene disruption of a gene encoding a \u03b3-butyrolactone autoregulator receptor from Kitasatospora setae","volume":"186","author":"Choi","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/1\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:09:33Z","timestamp":1760159373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/1\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["md19010029"],"URL":"https:\/\/doi.org\/10.3390\/md19010029","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]}}}