{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:31:26Z","timestamp":1790127086771,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2021-1396"],"award-info":[{"award-number":["075-15-2021-1396"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antibiotic resistance has been and remains a major problem in our society. The main solution to this problem is to search and study the mechanisms of antibiotic action. Many groups of secondary metabolites, including antimicrobial ones, are produced by the Actinomycetota phylum. The actinobacterial strains isolated from habitats that have not been well studied are of great interest. Due to high resource competition, antibiotics are now considered a \u2018trump card in the game of life\u2019 due to their presence in natural substrates with limited nutrients. Potentially, strains isolated from such habitats can be producers of novel or poorly studied antibiotics. In the current research, we identified the strain Streptomyces sp. AP22 from the soils of the Akhshatyrsky Gorge, which is capable of producing pentalenolactone. This study describes the phenotypic and morphological characteristics of Streptomyces sp. AP22 and its biological activity. Pentalenolactone is a known inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important enzyme involved in glycolysis. We identified a previously unknown mutation in the gapA gene encoding glyceraldehyde-3-phosphate dehydrogenase that confers resistance to this antibiotic compound. This antibiotic is not used in clinical practice, so its application as a selectable marker will not lead to the creation of pathogens resistant to clinically relevant antibiotics. In this case, the selectable marker is based on a genetic construct containing the glyceraldehyde-3-phosphate dehydrogenase gene with a resistance mutation. The use of this selectable marker can be applied to various genetic and molecular techniques, such as cloning and transformation. This can help to facilitate genetic and molecular biology studies of strains resistant to standard selectable markers such as kanamycin or ampicillin.<\/jats:p>","DOI":"10.3390\/ijms252413328","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T03:52:49Z","timestamp":1733975569000},"page":"13328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel Selectable Marker Sesquiterpenoid Antibiotic Pentalenolactone"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1425-1145","authenticated-orcid":false,"given":"Arina A.","family":"Nikandrova","sequence":"first","affiliation":[{"name":"Center for Molecular and Cellular Biology, 121205 Moscow, Russia"},{"name":"Department of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3355-327X","authenticated-orcid":false,"given":"Anna D.","family":"Petriakova","sequence":"additional","affiliation":[{"name":"Department of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton R.","family":"Izzi","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Biology, 121205 Moscow, Russia"},{"name":"School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garegin A.","family":"Petrosyan","sequence":"additional","affiliation":[{"name":"Department of Soil Science, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim N.","family":"Tashlitsky","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-5890","authenticated-orcid":false,"given":"Vera A.","family":"Alferova","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-0514","authenticated-orcid":false,"given":"Tatiana V.","family":"Panova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-3089","authenticated-orcid":false,"given":"Maria G.","family":"Khrenova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Bach Institute of Biochemistry, Federal Research Centre \u201cFundamentals of Biotechnology\u201d of the Russian Academy of Sciences, 119071 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-1221","authenticated-orcid":false,"given":"Mikhail V.","family":"Biryukov","sequence":"additional","affiliation":[{"name":"Department of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8943-5761","authenticated-orcid":false,"given":"Yuliya V.","family":"Zakalyukina","sequence":"additional","affiliation":[{"name":"Department of Soil Science, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7432-1574","authenticated-orcid":false,"given":"Maria I.","family":"Zvereva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1413-9559","authenticated-orcid":false,"given":"Dmitrii A.","family":"Lukianov","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Biology, 121205 Moscow, Russia"},{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8866-1863","authenticated-orcid":false,"given":"Petr V.","family":"Sergiev","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Biology, 121205 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Simeis, D., and Serra, S. (2021). Actinomycetes: A Never-Ending Source of Bioactive Compounds-An Overview on Antibiotics Production. Antibiotics, 10.","DOI":"10.3390\/antibiotics10050483"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MMBR.00019-15","article-title":"Taxonomy, Physiology, and Natural Products of Actinobacteria","volume":"80","author":"Barka","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mib.2019.10.008","article-title":"Antibiotics: Past, present and future","volume":"51","author":"Hutchings","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Silva, G.D.C., Kitano, I.T., Ribeiro, I.A.D.F., and Lacava, P.T. (2022). The Potential Use of Actinomycetes as Microbial Inoculants and Biopesticides in Agriculture. Front. Soil Sci., 2.","DOI":"10.3389\/fsoil.2022.833181"},{"key":"ref_5","unstructured":"English, A.R., Mcbride, T.J., and Lynch, J.E. (1956). PA 132, a new antibiotic. II. In vitro and in vivo studies. Antibiot. Annu., 676\u2013681."},{"key":"ref_6","first-page":"2737","article-title":"The structure of pentalenolactone (PA-132)","volume":"32","author":"Takeuchi","year":"1969","journal-title":"Tetrahedron Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Takahashi, Y., and Nakashima, T. (2018). Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics. Antibiotics, 7.","DOI":"10.3390\/antibiotics7020045"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Siddharth, S., and Vittal, R. (2018). Evaluation of Antimicrobial, Enzyme Inhibitory, Antioxidant and Cytotoxic Activities of Partially Purified Volatile Metabolites of Marine Streptomyces sp. S2A. Microorganisms., 6.","DOI":"10.3390\/microorganisms6030072"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1128\/AAC.02117-16","article-title":"Sorting Out Antibiotics\u2019 Mechanisms of Action: A Double Fluorescent Protein Reporter for High-Throughput Screening of Ribosome and DNA Biosynthesis Inhibitors","volume":"60","author":"Osterman","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/s41592-020-00971-x","article-title":"metaFlye: Scalable long-read metagenome assembly using repeat graphs","volume":"17","author":"Kolmogorov","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41587-020-0740-8","article-title":"Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra","volume":"39","author":"Nothias","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41592-019-0344-8","article-title":"SIRIUS 4: A rapid tool for turning tandem mass spectra into metabolite structure information","volume":"16","author":"Fleischauer","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13321-016-0115-9","article-title":"MetFrag relaunched: Incorporating strategies beyond in silico fragmentation","volume":"8","author":"Ruttkies","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1021\/ja111279h","article-title":"Genome mining in Streptomyces. Discovery of an unprecedented P450-catalyzed oxidative rearrangement that is the final step in the biosynthesis of pentalenolactone","volume":"133","author":"Zhu","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0003-9861(89)90006-4","article-title":"Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone: Kinetic and mechanistic studies","volume":"270","author":"Cane","year":"1989","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/282535a0","article-title":"Inhibition of spinach glyceraldehyde-3-phosphate dehydrogenases by pentalenolactone","volume":"282","author":"Mann","year":"1979","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nbt820","article-title":"Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis","volume":"21","author":"Ikeda","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1128\/jb.153.2.930-936.1983","article-title":"Characterization of two glyceraldehyde-3-phosphate dehydrogenase isoenzymes from the pentalenolactone producer Streptomyces arenae","volume":"153","author":"Maurer","year":"1983","journal-title":"J. Bacteriol."},{"key":"ref_22","first-page":"179","article-title":"Pentalenolactone-insensitive glyceraldehyde-3-phosphate dehydrogenase from Streptomyces arenae is closely related to GAPDH from thermostable eubacteria and plant chloroplasts","volume":"165","author":"Kannwischer","year":"1996","journal-title":"Arch. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0014-5793(72)80040-1","article-title":"Glyceraldehyde 3-phosphate dehydrogenase: Amino acid sequence of enzyme from baker\u2019s yeast","volume":"22","author":"Harris","year":"1972","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ijbiomac.2022.08.001","article-title":"Characteristics and molecular identification of glyceraldehyde-3-phosphate dehydrogenases in poplar","volume":"219","author":"Wei","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.GPP3-0057-2018","article-title":"Antibioticresistance and the MRSA problem","volume":"7","author":"Vestergaard","year":"2019","journal-title":"Microbiol. Spectrum."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1021\/bi060419n","article-title":"A Gene Cluster for Biosynthesis of the Sesquiterpenoid Antibiotic Pentalenolactone in Streptomyces avermitilis","volume":"45","author":"Tetzlaff","year":"2006","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jang, C.W., and Magnuson, T. (2013). A novel selection marker for efficient DNA cloning and recombineering in E. coli. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057075"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1073\/pnas.75.8.3737","article-title":"Nucleotide sequence of the ampicillin resistance gene of Escherichia coli plasmid pBR322","volume":"75","author":"Sutcliffe","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1073\/pnas.71.9.3455","article-title":"Plasmid ColEl as a molecular vehicle for cloning and amplification of DNA","volume":"71","author":"Hershfield","year":"1974","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4161\/mge.23089","article-title":"Various pathways leading to the acquisition of antibiotic resistance by natural transformation","volume":"2","author":"Domingues","year":"2012","journal-title":"Mob. Genet. Elem."},{"key":"ref_32","first-page":"10","article-title":"Selectable Markers for Use in Genetic Manipulation of Extensively Drug-Resistant (XDR) Acinetobacter baumannii HUMC1","volume":"2","author":"Luna","year":"2012","journal-title":"mSphere"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/mmy.39.1.151.154","article-title":"A new dominant selectable marker for use in Cryptococcus neoformans","volume":"39","author":"McDade","year":"2001","journal-title":"Med. Mycol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Khrenova, M.G., Panova, T.V., Rodin, V.A., Kryakvin, M.A., Lukyanov, D.A., Osterman, I.A., and Zvereva, M.I. (2022). Nanopore Sequencing for De Novo Bacterial Genome Assembly and Search for Single-Nucleotide Polymorphism. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158569"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wick, R.R., Judd, L.M., and Holt, K.E. (2019). Performance of neural network basecalling tools for Oxford Nanopore sequencing. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1727-y"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zakalyukina, Y.V., Pavlov, N.A., Lukianov, D.A., Marina, V.I., Belozerova, O.A., Tashlitsky, V.N., Guglya, E.B., Osterman, I.A., and Biryukov, M.V. (2022). A New Albomycin-Producing Strain of Streptomyces globisporus subsp. globisporus May Provide Protection for Ants Messor structor. Insects, 13.","DOI":"10.3390\/insects13111042"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13328\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:53:16Z","timestamp":1760115196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,12]]},"references-count":36,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413328"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413328","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,12]]}}}