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Diversity of Polyketide Synthases and Nonribosomal Peptide Synthetases Revealed Through Metagenomic Analysis of a Deep Oligotrophic Cave

  • Environmental Microbiology
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Abstract

Caves are considered to be extreme and challenging environments. It is believed that the ability of microorganisms to produce secondary metabolites enhances their survivability and adaptiveness in the energy-starved cave environment. Unfortunately, information on the genetic potential for the production of secondary metabolites, such as polyketides and nonribosomal peptides, is limited. In the present study, we aimed to identify and characterize genes responsible for the production of secondary metabolites in the microbial community of one of the deepest caves in the world, Krubera-Voronja Cave (43.4184 N 40.3083 E, Western Caucasus). The analysed sample materials included sediments, drinkable water from underground camps, soil and clay from the cave walls, speleothems and coloured spots from the cave walls. The type II polyketide synthases (PKSs) ketosynthases α and β and the adenylation domains of nonribosomal peptide synthetases (NRPSs) were investigated using a metagenomic approach. Taxonomic diversity analysis showed that most PKS sequences could be attributed to Actinobacteria followed by unclassified bacteria and Acidobacteria, while the NRPS sequences were more taxonomically diverse and could be assigned to Proteobacteria, Actinobacteria, Cyanobacteria, Firmicutes, Chloroflexi, etc. Only three putative metabolites could be predicted: an angucycline group polyketide, a massetolide A-like cyclic lipopeptide and a surfactin-like lipopeptide. The absolute majority of PKS and NRPS sequences showed low similarity with the sequences of the reference biosynthetic pathways, suggesting that these sequences could be involved in the production of novel secondary metabolites.

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References

  1. Ghosh S, Kuisiene N, Cheeptham N (2017) The cave microbiome as a source for drug discovery: reality or pipe dream? Biochem. Pharmacol. 134:18–34. https://doi.org/10.1016/j.bcp.2016.11.018

    Article  CAS  PubMed  Google Scholar 

  2. Adam D, Maciejewska M, Naȏme A, Martinet L, Coppieters W, Karim L, Baurain D, Rigali S (2018) Isolation, characterization, and antibacterial activity of hard-to-culture actinobacteria from cave moonmilk deposits. Antibiotics 7:28. https://doi.org/10.3390/antibiotics7020028

    Article  CAS  PubMed Central  Google Scholar 

  3. Belyagoubi L, Belyagoubi-Benhammou N, Jurado V, Dupont J, Lacoste S, Djebbah F, Ounadjela FZ, Benaissa S, Habi S, Abdelouahid DE, Saiz-Jimenez C (2018) Antimicrobial activities of culturable microorganisms (actinomycetes and fungi) isolated from Chaabe Cave, Algeria. Int. J. Speleol. 47:189–199. https://doi.org/10.5038/1827-806X.47.2.2148

    Article  Google Scholar 

  4. Duo JL, Cha QY, Zhou XK, Zhang TK, Qin SC, Yang PX, Zhu ML, Mo MH, Duan YQ (2019) Aquabacter cavernae sp. nov., a bacterium isolated from cave soil. Int. J. Syst. Evol. Microbiol. 69:3716–3722. https://doi.org/10.1099/ijsem.0.003585

    Article  CAS  PubMed  Google Scholar 

  5. Wiseschart A, Mhuanthong W, Tangphatsornruang S, Chantasingh D, Pootanakit K (2019) Shotgun metagenomic sequencing from Manao-Pee cave, Thailand, reveals insight into the microbial community structure and its metabolic potential. BMC Microbiol. 19:144. https://doi.org/10.1186/s12866-019-1521-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fang BZ, Han MX, Jiao JY, Xie YG, Zhang XT, Liu L, Zhang ZT, Xiao M, Li WJ (2020) Streptomyces cavernae sp. nov., a novel actinobacterium isolated from a karst cave sediment sample. Int. J. Syst. Evol. Microbiol. 70:120–125. https://doi.org/10.1099/ijsem.0.003724

    Article  CAS  PubMed  Google Scholar 

  7. Narsing Rao MP, Dong ZY, Kan Y, Zhang K, Fang BZ, Xiao M, Kang YQ, Li WJ (2020) Description of Paenibacillus antri sp. nov. and Paenibacillus mesophilus sp. nov., isolated from cave soil. Int. J. Syst. Evol. Microbiol. 70:1048–1054. https://doi.org/10.1099/ijsem.0.003870

    Article  CAS  PubMed  Google Scholar 

  8. Zhou XK, Huang Y, Li M, Zhang XF, Wei YQ, Qin SC, Zhang TK, Wang XJ, Liu JJ, Wang L, Liu ZY, Mo MH (2020) Asticcacaulis tiandongensis sp. nov., a new member of the genus Asticcacaulis, isolated from a cave soil sample. Int. J. Syst. Evol. Microbiol. 70:687–692. https://doi.org/10.1099/ijsem.0.003818

    Article  CAS  PubMed  Google Scholar 

  9. Avguštin JA, Petrič P, Pašić L (2019) Screening the cultivable cave microbial mats for the production of antimicrobial compounds and antibiotic resistance. Int. J. Speleol. 48:295–303. https://doi.org/10.5038/1827-806X.48.3.2272

    Article  Google Scholar 

  10. De Mandal S, Chatterjee R, Kumar NS (2017) Dominant bacterial phyla in caves and their predicted functional roles in C and N cycle. BMC Microbiol. 17:90. https://doi.org/10.1186/s12866-017-1002-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. D’Auria G, Artacho A, Rojas RA, Bautista JS, Méndez R, Gamboa MT, Gamboa JR, Gómez-Cruz R (2018) Metagenomics of bacterial diversity in Villa Luz caves with sulfur water springs. Genes 9:55. https://doi.org/10.3390/genes9010055

    Article  CAS  PubMed Central  Google Scholar 

  12. Busquets A, Fornós JJ, Zafra F, Lalucat J, Merino A (2014) Microbial communities in a coastal cave: Cova des Pas de Vallgornera (Mallorca, Western Mediterranean). Int. J. Speleol. 43:205–216. https://doi.org/10.5038/1827-806X.43.2.8

    Article  Google Scholar 

  13. Kumaresan D, Wischer D, Stephenson J, Hillebrand-Voiculescu A, Murrell JC (2014) Microbiology of Movile Cave - a chemolithoautotrophic ecosystem. Geomicrobiol J. 31:186–193. https://doi.org/10.1080/01490451.2013.839764

    Article  CAS  Google Scholar 

  14. Ortiz M, Legatzki A, Neilson JW, Fryslie B, Nelson WM, Wing RA, Soderlund CA, Pryor BM, Maier RM (2014) Making a living while starving in the dark: metagenomic insights into the energy dynamics of a carbonate cave. ISME J 8:478–491. https://doi.org/10.1038/ismej.2013.159

    Article  CAS  PubMed  Google Scholar 

  15. Zepeda Mendoza ML, Lundberg J, Ivarsson M, Campos P, Nylander JAA, Sallstedt T, Dalen L (2016) Metagenomic analysis from the interior of a speleothem in Tjuv-Ante’s Cave, Northern Sweden. PLoS One 11:e0151577. https://doi.org/10.1371/journal.pone.0151577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Waring CL, Hankin SI, Griffith DWT, Kertesz MA, Kobylski V, Wilson NL, Coleman NV, Kettlewell G, Zlot R, Bosse M, Bell G (2017) Seasonal total methane depletion in limestone caves. Sci. Rep. 7:8314. https://doi.org/10.1038/s41598-017-07769-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Montano ET, Henderson LO (2013) Studies of antibiotic production by cave bacteria. In: Cheeptham N (ed) Cave microbiomes: a novel resource for drug discovery. SpringerBriefs in Microbiology, vol 1. Springer, New York, pp 109–130. https://doi.org/10.1007/978-1-4614-5206-5_6

    Chapter  Google Scholar 

  18. Bauer MA, Kainz K, Carmona-Gutierrez D, Madeo F (2018) Microbial wars: competition in ecological niches and within the microbiome. Microb Cell 5:215–219. https://doi.org/10.15698/mic2018.05.628

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sengupta S, Chattopadhyay MK, Grossart HP (2013) The multifaceted roles of antibiotics and antibiotic resistance in nature. Front. Microbiol. 4:47. https://doi.org/10.3389/fmicb.2013.00047

    Article  PubMed  PubMed Central  Google Scholar 

  20. Stubbendieck RM, Straight PD (2016) Multifaceted interfaces of bacterial competition. J. Bacteriol. 98:2145–2155. https://doi.org/10.1128/JB.00275-16

    Article  CAS  Google Scholar 

  21. Chevrette MG, Currie CR (2019) Emerging evolutionary paradigms in antibiotic discovery. J. Ind. Microbiol. Biotechnol. 46:257–271. https://doi.org/10.1007/s10295-018-2085-6

    Article  CAS  PubMed  Google Scholar 

  22. Jiang ZK, Guo L, Chen C, Liu SW, Zhang L, Dai SJ, He QY, You XF, Hu XX, Tuo L, Jiang W, Sun CH (2015) Xiakemycin A, a novel pyranonaphthoquinone antibiotic, produced by the Streptomyces sp. CC8-201 from the soil of a karst cave. J Antibiot. 68:771–774. https://doi.org/10.1038/ja.2015.70

    Article  CAS  Google Scholar 

  23. Axenov-Gribanov DV, Voytsekhovskaya IV, Tokovenko BT, Protasov ES, Gamaiunov SV, Rebets YV, Luzhetskyy AN, Timofeyev MA (2016) Actinobacteria isolated from an underground lake and moonmilk speleothem from the biggest conglomeratic karstic cave in Siberia as sources of novel biologically active compounds. PLoS One 11:e0149216. https://doi.org/10.1371/journal.pone.0152957

    Article  CAS  PubMed  Google Scholar 

  24. Ghosh S, Kam G, Nijjer M, Stenner C, Cheeptham N (2020) Culture dependent analysis of bacterial diversity in Canada’s Raspberry Rising Cave revealed antimicrobial properties. Int. J. Speleol. 49:43–53. https://doi.org/10.5038/1827-806X.49.1.2291

    Article  Google Scholar 

  25. Bhullar K, Waglechner N, Pawlowski A, Koteva K, Banks ED, Johnston MD, Barton HA, Wright GD (2012) Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS One 7:e34953. https://doi.org/10.1371/journal.pone.0034953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gaálová B, Donauerová A, Seman M, Bujdáková H (2014) Identification and β-lactam resistance in aquatic isolates of Enterobacter cloacae and their status in microbiota of Domica Cave in Slovak Karst (Slovakia). Int. J. Speleol. 43:69–77. https://doi.org/10.5038/1827-806X.43.1.7

    Article  Google Scholar 

  27. Pawlowski AC, Wang W, Koteva K, Barton HA, McArthur AG, Wright GD (2016) A diverse intrinsic antibiotic resistome from a cave bacterium. Nat. Commun. 7:13803. https://doi.org/10.1038/ncomms13803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lavoie K, Ruhumbika T, Bawa A, Whitney A, de Ondarza J (2017) High levels of antibiotic resistance but no antibiotic production detected along a gypsum gradient in Great Onyx Cave, KY, USA. Diversity 9:42. https://doi.org/10.3390/d9040042

    Article  CAS  Google Scholar 

  29. Miller IJ, Chevrette MG, Kwan JC (2017) Interpreting microbial biosynthesis in the genomic age: biological and practical considerations. Mar Drugs 15:165. https://doi.org/10.3390/md15060165

    Article  CAS  PubMed Central  Google Scholar 

  30. Libis V, Antonovsky N, Zhang M, Shang Z, Montiel D, Maniko J, Ternei MA, Calle PY, Lemetre C, Owen JG, Brady SF (2019) Uncovering the biosynthetic potential of rare metagenomic DNA using co-occurrence network analysis of targeted sequences. Nat. Commun. 10:3848. https://doi.org/10.1038/s41467-019-11658-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Maciejewska M, Adam D, Martinet L, Naômé A, Całusińska M, Delfosse P, Carnol M, Barton HA, Hayette MP, Smargiasso N, De Pauw E, Hanikenne M, Baurain D, Rigali S (2016) A phenotypic and genotypic analysis of the antimicrobial potential of cultivable Streptomyces isolated from cave moonmilk deposits. Front. Microbiol. 7:1455. https://doi.org/10.3389/fmicb.2016.01455

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bukelskis D, Dabkeviciene D, Lukoseviciute L, Bucelis A, Kriaučiūnas I, Lebedeva J, Kuisiene N (2019) Screening and transcriptional analysis of polyketide synthases and non-ribosomal peptide synthetases in bacterial strains from Krubera-Voronja cave. Front. Microbiol. 10:2149. https://doi.org/10.3389/fmicb.2019.02149

    Article  PubMed  PubMed Central  Google Scholar 

  33. Gosse JT, Ghosh S, Sproule A, Overy D, Cheeptham N, Boddy CN (2019) Whole genome sequencing and metabolomic study of cave Streptomyces isolates ICC1 and ICC4. Front. Microbiol. 10:1020. https://doi.org/10.3389/fmicb.2019.01020

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wiseschart A, Mhuanthong W, Thongkam P, Tangphatsornruang S, Chantasingh D, Pootanakit K (2018) Bacterial diversity and phylogenetic analysis of type II polyketide synthase gene from Manao-Pee Cave, Thailand. Geomicrobiol J. 35:518–527. https://doi.org/10.1080/01490451.2017.1411993

    Article  CAS  Google Scholar 

  35. Riquelme C, Enes Dapkevicius ML, Miller AZ, Charlop-Powers Z, Brady S, Mason C, Cheeptham N (2017) Biotechnological potential of Actinobacteria from Canadian and Azorean volcanic caves. Appl. Microbiol. Biotechnol. 101:843–857. https://doi.org/10.1007/s00253-016-7932-7

    Article  CAS  PubMed  Google Scholar 

  36. Cuadrat RRC, Ionescu D, Dávila AMR, Grossart H-P (2018) Recovering genomics clusters of secondary metabolites from lakes using genome-resolved metagenomics. Front. Microbiol. 9:251. https://doi.org/10.3389/fmicb.2018.00251

    Article  PubMed  PubMed Central  Google Scholar 

  37. Klusaite A, Vickackaite V, Vaitkeviciene B, Karnickaite R, Bukelskis D, Kieraite-Aleksandrova I, Kuisiene N (2016) Characterization of antimicrobial activity of culturable bacteria isolated from Krubera-Voronja Cave. Int. J. Speleol. 45:275–287. https://doi.org/10.5038/1827-806X.45.3.1978

    Article  Google Scholar 

  38. Chevrette MG, Handelsman J (2020) From metagenomes to molecules: innovations in functional metagenomics unlock hidden chemistry in the human microbiome. Biochemistry 59:729–730. https://doi.org/10.1021/acs.biochem.0c00033

    Article  CAS  PubMed  Google Scholar 

  39. Kieraite-Aleksandrova I, Aleksandrovas V, Kuisiene N (2015) Down into the earth: microbial diversity of the deepest cave of the world. Biologia 70:989–1002. https://doi.org/10.1515/biolog-2015-0127

    Article  Google Scholar 

  40. Studholme DJ, Jackson RA, Leak DJ (1999) Phylogenetic analysis of transformable strains of thermophilic Bacillus species. FEMS Microbiol. Lett. 172:85–90. https://doi.org/10.1111/j.1574-6968.1999.tb13454.x

    Article  CAS  PubMed  Google Scholar 

  41. Kuisiene N, Jomantiene R, Valiunas D, Chitavichius D (2002) Characterization of thermophilic proteolytic spore-forming bacteria from a geothermal site in Lithuania based on 16S rDNA RFLP and ITS-PCR analyses. Microbiology 71:712–716. https://doi.org/10.1023/A:1021440208887

    Article  CAS  Google Scholar 

  42. Tambadou F, Lanneluc I, Sablé S, Klein GL, Doghri I, Sopéna V, Didelot S, Barthélémy C, Thiéry V, Chevrot R (2014) Novel nonribosomal peptide synthetase (NRPS) genes sequenced from intertidal mudflat bacteria. FEMS Microbiol. Lett. 357:123–130. https://doi.org/10.1111/1574-6968.12532

    Article  CAS  PubMed  Google Scholar 

  43. Ayuso-Sacido A, Genilloud O (2005) New PCR primers for the screening of NRPS and PKS-I systems in actinomycetes: detection and distribution of these biosynthetic gene sequences in major taxonomic groups. Microb. Ecol. 49:10–24. https://doi.org/10.1007/s00248-004-0249-6

    Article  CAS  PubMed  Google Scholar 

  44. Wood SA, Kirby BM, Goodwin CM, Le Roes M, Meyers PR (2007) PCR screening reveals unexpected antibiotic biosynthetic potential in Amycolatopsis sp. strain UM16. J. Appl. Microbiol. 102:245–253. https://doi.org/10.1111/j.1365-2672.2006.03043.x

    Article  CAS  PubMed  Google Scholar 

  45. Metsä-Ketelä M, Salo V, Halo L, Hautala A, Hakala J, Mäntsälä P, Ylihonko K (1999) An efficient approach for screening minimal PKS genes from Streptomyces. FEMS Microbiol. Lett. 180:1–6. https://doi.org/10.1111/j.1574-6968.1999.tb08770.x

    Article  PubMed  Google Scholar 

  46. Jenke-Kodama H, Dittmann E (2009) Evolution of metabolic diversity: insights from microbial polyketide synthases. Phytochemistry 70:1858–1866. https://doi.org/10.1016/j.phytochem.2009.05.021

    Article  CAS  PubMed  Google Scholar 

  47. Chevrette MG, Gutiérrez-García K, Selem-Mojica N, Aguilar-Martínez C, Yañez-Olvera A, Ramos-Aboites HE, Hoskisson PA, Barona-Gómez F (2020) Evolutionary dynamics of natural product biosynthesis in bacteria. Nat. Prod. Rep. 37:566–599. https://doi.org/10.1039/c9np00048h

    Article  CAS  PubMed  Google Scholar 

  48. Chen S, Zhou Y, Chen Y, Gu J (2018) fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34:i884–i890. https://doi.org/10.1093/bioinformatics/bty560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, Buxton S, Cooper A, Markowitz S, Duran C, Thierer T, Ashton B, Meintjes P, Drummond A (2012) Geneious basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28:1647–1649. https://doi.org/10.1093/bioinformatics/bts199

    Article  PubMed  PubMed Central  Google Scholar 

  50. Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R (2011) UCHIME improves sensitivity and speed of chimera detection. Bioinformatics 27:2194–2200. https://doi.org/10.1093/bioinformatics/btr381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kautsar SA, Blin K, Shaw S, Navarro-Muñoz JC, Terlouw BR, van der Hooft JJJ, van Santen JA, Tracanna V, Suarez Duran HG, Pascal Andreu V, Selem-Mojica N, Alanjary M, Robinson SL, Lund G, Epstein SC, Sisto AC, Charkoudian LK, Collemare J, Linington RG, Weber T, Medema MH (2020) MIBiG 2.0: a repository for biosynthetic gene clusters of known function. Nucleic Acids Res. 48:D454–D458. https://doi.org/10.1093/nar/gkz882

    Article  PubMed  Google Scholar 

  52. Conway KR, Boddy CN (2013) ClusterMine360: a database of microbial PKS/NRPS biosynthesis. Nucleic Acids Res. 41:D402–D407. https://doi.org/10.1093/nar/gks993

    Article  CAS  PubMed  Google Scholar 

  53. Meyer F, Paarmann D, D’Souza M, Olson R, Glass EM, Kubal M, Paczian T, Rodriguez A, Stevens R, Wilke A, Wilkening J, Edwards RA (2008) The metagenomics RAST sever – a public resource for the automatic phylogenetic and functional analysis of metagenomes. BMC Bioinformatics 9:386. https://doi.org/10.1186/1471-2105-9-386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4:406–425. https://doi.org/10.1093/oxfordjournals.molbev.a040454

    Article  CAS  PubMed  Google Scholar 

  55. Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33:1870–1874. https://doi.org/10.1093/molbev/msw054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Letunic I, Bork P (2019) Interactive Tree of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res. 47:W256–W259. https://doi.org/10.1093/nar/gkz239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ziemert N, Podell S, Penn K, Badger JH, Allen E, Jensen PR (2012) The natural product domain seeker NaPDoS: a phylogeny based bioinformatics tool to classify secondary metabolite gene diversity. PLoS One 7:e34064. https://doi.org/10.1371/journal.pone.0034064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Prieto C, García-Estrada C, Lorenzana D, Martín JF (2012) NRPSsp: non-ribosomal peptide synthase substrate predictor. Bioinformatics 28:426–427. https://doi.org/10.1093/bioinformatics/btr659

    Article  CAS  PubMed  Google Scholar 

  59. Della Sala G, Hochmuth T, Teta R, Costantino V, Mangoni A (2014) Polyketide synthases in the microbiome of the marine sponge Plakortis halichondrioides: a metagenomic update. Mar Drugs 12:5425–5440. https://doi.org/10.3390/md12115425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Müller CA, Oberauner-Wappis L, Peyman A, Amos GCA, Wellington EMH, Berg G (2015) Mining for nonribosomal peptide synthetase and polyketide synthase genes revealed a high level of diversity in the Sphagnum bog metagenome. Appl. Environ. Microbiol. 81:5064–5072. https://doi.org/10.1128/AEM.00631-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wei Y, Zhang L, Zhou Z, Yan X (2018) Diversity of gene clusters for polyketide and nonribosomal peptide biosynthesis revealed by metagenomic analysis of the Yellow Sea sediment. Front. Microbiol. 9:295. https://doi.org/10.3389/fmicb.2018.00295

    Article  PubMed  PubMed Central  Google Scholar 

  62. Hershey OS, Barton HA (2018) The microbial diversity of caves. In: Moldovan OT, Kováč L, Halse S (eds). Springer International Publishing, Cave ecology, pp 69–90. https://doi.org/10.1007/978-3-319-98852-8

    Chapter  Google Scholar 

  63. Oliveira C, Gunderman L, Coles CA, Lochmann J, Parks M, Ballard E, Glazko G, Rahmatallah Y, Tackett AJ, Thomas DJ (2017) 16S rRNA gene-based metagenomic analysis of Ozark Cave bacteria. Diversity (Basel) 9:31. https://doi.org/10.3390/d9030031

    Article  CAS  Google Scholar 

  64. Zhu H-Z, Zhang Z-F, Zhou N, Jiang C-Y, Wang B-J, Cai L, Liu S-J (2019) Diversity, distribution and co-occurrence patterns of bacterial communities in a karst cave system. Front. Microbiol. 10:1726. https://doi.org/10.3389/fmicb.2019.01726

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ziemert N, Jensen PR (2012) Phylogenetic approaches to natural product structure prediction. Methods Enzymol. 517:161–182. https://doi.org/10.1016/b978-0-12-404634-4.00008-5

    Article  PubMed  PubMed Central  Google Scholar 

  66. Gui C, Liu Y, Zhou Z, Zhang S, Hu Y, Gu YC, Huang H, Ju J (2018) Angucycline glycosides from mangrove-derived Streptomyces diastaticus subsp. SCSIO GJ056. Mar Drugs 16:185. https://doi.org/10.3390/md16060185

    Article  CAS  PubMed Central  Google Scholar 

  67. Crits-Christoph A, Diamond S, Butterfield CN, Thomas BC, Banfield JF (2018) Novel soil bacteria possess diverse genes for secondary metabolite biosynthesis. Nature 558:440–444. https://doi.org/10.1038/s41586-018-0207-y

    Article  CAS  PubMed  Google Scholar 

  68. Kielak AM, Barreto CC, Kowalchuk GA, van Veen JA, Kuramae EE (2016) The ecology of Acidobacteria: moving beyond genes and genomes. Front. Microbiol. 7:744. https://doi.org/10.3389/fmicb.2016.00744

    Article  PubMed  PubMed Central  Google Scholar 

  69. Radjasa OK, Wiese J, Sabdono A, Imhoff JF (2008) Corals as source of bacteria with antimicrobial activity. J Coast Dev 11:121–130

    Google Scholar 

  70. McErlean M, Overbay J, Van Lanen S (2019) Refining and expanding nonribosomal peptide synthetase function and mechanism. J. Ind. Microbiol. Biotechnol. 46:493–513. https://doi.org/10.1007/s10295-018-02130-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Khayatt BI, Overmars L, Siezen R, Francke C (2013) Classification of the adenylation and acyl-transferase activity of NRPS and PKS systems using ensembles of substrate specific Hidden Markov Models. PLoS One 8:e62136. https://doi.org/10.1371/journal.pone.0062136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Flissi A, Ricart E, Campart C, Chevalier M, Dufresne Y, Michalik J, Jacques P, Flahaut C, Lisacek F, Leclère V, Pupin M (2020) Norine: update of the nonribosomal peptide resource. Nucleic Acids Res. 48:D465–D469. https://doi.org/10.1093/nar/gkz1000

    Article  CAS  PubMed  Google Scholar 

  73. Hou J, Robbel L, Marahiel MA (2011) Identification and characterization of the lysobactin biosynthetic gene cluster reveals mechanistic insights into an unusual termination module architecture. Chem. Biol. 18:655–664. https://doi.org/10.1016/j.chembiol.2011.02.012

    Article  CAS  PubMed  Google Scholar 

  74. Ringel MT, Brüser T (2018) The biosynthesis of pyoverdines. Microb Cell 5:424–437. https://doi.org/10.15698/mic2018.10.649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sendra A, Reboleira ASPS (2012) The world’s deepest subterranean community Krubera-Voronja Cave (Western Caucasus). Int. J. Speleol. 41:221–230. https://doi.org/10.5038/1827-806X.41.2.9

    Article  Google Scholar 

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This work was supported by the Research Council of Lithuania (grant no. S-MIP-17-21).

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Lukoseviciute, L., Lebedeva, J. & Kuisiene, N. Diversity of Polyketide Synthases and Nonribosomal Peptide Synthetases Revealed Through Metagenomic Analysis of a Deep Oligotrophic Cave. Microb Ecol 81, 110–121 (2021). https://doi.org/10.1007/s00248-020-01554-1

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