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2000
Volume 15, Issue 7
  • ISSN: 2210-3155
  • E-ISSN: 2210-3163

Abstract

Introduction

is a genus of bacteria that has gained recent attention due to its unique ability to produce bioactive compounds that possess potential antimicrobial properties.

Methods

In this study, we isolated two cyclic dipeptides (CDPs) from sp. obtained from a soil sample.

Results

The isolated sp. exhibited inhibitory activity against a filamentous indicator bacterium and a violacein-producing sp. Cultivation of sp. TAJX1902 was carried out using rich medium broth and agar to facilitate the extraction of metabolites. The isolated compounds were characterized through spectroscopic techniques. GCMS analysis of the crude extract revealed the presence of bioactive cyclic dipeptides.

Conclusion

The structures of the isolated CDPs were determined as acylated cyclo(D-phenylalanine-4-hydroxy-D-proline) () and cyclo(D-phenylalanine-D-proline) (). Furthermore, two additional metabolites, 2,4-dihydroxypyrimidine () and 2,4-dihydroxy-5-methylpyrimidine (), were identified and verified through NMR spectral analysis.

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References

  1. Antibiotic resistance threats in the United States2019Available from: https://ndc.services.cdc.gov/wp-content/uploads/Antibiotic-Resistance-Threats-in-the-United-States-2019.pdf
  2. ViswanathanV.K. Off-label abuse of antibiotics by bacteria.Gut Microbes2014513410.4161/gmic.28027 24637595
    [Google Scholar]
  3. MunitaJ.M. AriasC.A. Mechanisms of antibiotic resistance.Microbiol. Spectr.2016424.2.1510.1128/microbiolspec.VMBF‑0016‑2015 27227291
    [Google Scholar]
  4. Van BoeckelT.P. GandraS. AshokA. CaudronQ. GrenfellB.T. LevinS.A. LaxminarayanR. Global antibiotic consumption 2000 to 2010: An analysis of national pharmaceutical sales data.Lancet Infect. Dis.201414874275010.1016/S1473‑3099(14)70780‑7 25022435
    [Google Scholar]
  5. RossiterS.E. FletcherM.H. WuestW.M. Natural products as platforms to overcome antibiotic resistance.Chem. Rev.201711719124151247410.1021/acs.chemrev.7b00283 28953368
    [Google Scholar]
  6. McMurryL. PetrucciR.E. LevyS.B. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc. Natl. Acad. Sci. USA19807773974397710.1073/pnas.77.7.3974 7001450
    [Google Scholar]
  7. BartonD. Meth-CohnO. Comprehensive Natural Products Chemistry.1st edNewnes1999
    [Google Scholar]
  8. ChibaleK. Economic drug discovery and rational medicinal chemistry for tropical diseases.Pure Appl. Chem.200577111957196410.1351/pac200577111957
    [Google Scholar]
  9. DemainA.L. Importance of microbial natural products and the need to revitalize their discovery.J. Ind. Microbiol. Biotechnol.201441218520110.1007/s10295‑013‑1325‑z 23990168
    [Google Scholar]
  10. NewmanD.J. CraggG.M. SnaderK.M. Natural products as sources of new drugs over the period 1981-2002.J. Nat. Prod.20036671022103710.1021/np030096l 12880330
    [Google Scholar]
  11. CraggG.M. NewmanD.J. Natural products: A continuing source of novel drug leads.Biochim. Biophys. Acta, Gen. Subj.2013183063670369510.1016/j.bbagen.2013.02.008 23428572
    [Google Scholar]
  12. Abdel-RazekA.S. El-NaggarM.E. AllamA. MorsyO.M. OthmanS.I. Microbial natural products in drug discovery.Processes (Basel)20208447010.3390/pr8040470
    [Google Scholar]
  13. HuY. PhelanV. NtaiI. FarnetC.M. ZazopoulosE. BachmannB.O. Benzodiazepine biosynthesis in Streptomyces refuineus. Chem. Biol.200714669170110.1016/j.chembiol.2007.05.009 17584616
    [Google Scholar]
  14. Ntie-KangF. SvozilD. An enumeration of natural products from microbial, marine and terrestrial sources.Phys. Sci. Rev.2020582018012110.1515/psr‑2018‑0121
    [Google Scholar]
  15. KramerJ. ÖzkayaÖ. KümmerliR. Bacterial siderophores in community and host interactions.Nat. Rev. Microbiol.202018315216310.1038/s41579‑019‑0284‑4 31748738
    [Google Scholar]
  16. ManivasaganP. VenkatesanJ. SivakumarK. KimS.K. Pharmaceutically active secondary metabolites of marine actinobacteria.Microbiol. Res.2014169426227810.1016/j.micres.2013.07.014 23958059
    [Google Scholar]
  17. DangT. SüssmuthR.D. Bioactive peptide natural products as lead structures for medicinal use.Acc. Chem. Res.20175071566157610.1021/acs.accounts.7b00159 28650175
    [Google Scholar]
  18. WangJ. ZhangR. ChenX. SunX. YanY. ShenX. YuanQ. Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases.Microb. Cell Fact.202019111010.1186/s12934‑020‑01367‑4 32448179
    [Google Scholar]
  19. ZhaoP. XueY. GaoW. LiJ. ZuX. FuD. FengS. BaiX. ZuoY. LiP. Actinobacteria–derived peptide antibiotics since 2000.Peptides2018103485910.1016/j.peptides.2018.03.011 29567053
    [Google Scholar]
  20. WalshC.T. O’BrienR.V. KhoslaC. Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds.Angew. Chem. Int. Ed.201352287098712410.1002/anie.201208344 23729217
    [Google Scholar]
  21. OrtegaM.A. van der DonkW.A. New insights into the biosynthetic logic of ribosomally synthesized and post-translationally modified peptide natural products.Cell Chem. Biol.2016231314410.1016/j.chembiol.2015.11.012 26933734
    [Google Scholar]
  22. WalkerJ.A. HamlishN. TytlaA. BrauerD.D. FrancisM.B. SchepartzA. Redirecting RiPP biosynthetic enzymes to proteins and backbone-modified substrates.ACS Cent. Sci.20228447348210.1021/acscentsci.1c01577 35505866
    [Google Scholar]
  23. ImaniA.S. FreemanM.F. RiPPing apart the rules for peptide natural products.Synth. Syst. Biotechnol.201832818210.1016/j.synbio.2018.03.002 29900419
    [Google Scholar]
  24. AndrewB. ScottL. Practical Medicinal Chemistry with Macrocycles; Marsault, E. PetersonM.L. Hoboken, NJ, USAJohn Wiley & Sons, Inc.201710.1002/9781119092599
    [Google Scholar]
  25. DandapaniS. MarcaurelleL.A. Grand Challenge Commentary: Accessing new chemical space for ‘undruggable’ targets.Nat. Chem. Biol.201061286186310.1038/nchembio.479 21079589
    [Google Scholar]
  26. JooS.H. Cyclic peptides as therapeutic agents and biochemical tools.Biomol. Ther. (Seoul)2012201192610.4062/biomolther.2012.20.1.019 24116270
    [Google Scholar]
  27. BhatA. RobertsL.R. DwyerJ.J. Lead discovery and optimization strategies for peptide macrocycles.Eur. J. Med. Chem.20159447147910.1016/j.ejmech.2014.07.083 25109255
    [Google Scholar]
  28. ParkS.C. ParkY. HahmK.S. The role of antimicrobial peptides in preventing multidrug-resistant bacterial infections and biofilm formation.Int. J. Mol. Sci.20111295971599210.3390/ijms12095971 22016639
    [Google Scholar]
  29. KitagakiJ. ShiG. MiyauchiS. MurakamiS. YangY. Cyclic depsipeptides as potential cancer therapeutics.Anticancer Drugs201526325927110.1097/CAD.0000000000000183 25419631
    [Google Scholar]
  30. GavrishE. SitC.S. CaoS. KandrorO. SpoeringA. PeoplesA. LingL. FettermanA. HughesD. BissellA. TorreyH. AkopianT. MuellerA. EpsteinS. GoldbergA. ClardyJ. LewisK. Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2.Chem. Biol.201421450951810.1016/j.chembiol.2014.01.014 24684906
    [Google Scholar]
  31. RisdianC. MozefT. WinkJ. Biosynthesis of polyketides in Streptomyces. Microorganisms20197512410.3390/microorganisms7050124 31064143
    [Google Scholar]
  32. LingL.L. SchneiderT. PeoplesA.J. SpoeringA.L. EngelsI. ConlonB.P. MuellerA. SchäberleT.F. HughesD.E. EpsteinS. JonesM. LazaridesL. SteadmanV.A. CohenD.R. FelixC.R. FettermanK.A. MillettW.P. NittiA.G. ZulloA.M. ChenC. LewisK. A new antibiotic kills pathogens without detectable resistance.Nature2015517753545545910.1038/nature14098 25561178
    [Google Scholar]
  33. RanjaniA. DhanasekaranD. GopinathP.M. An introduction to actinobacteria.Actinobacteria - Basics and Biotechnological Applications. DhanasekaranD. JiangY. IntechOpen201610.5772/62329
    [Google Scholar]
  34. IgarashiY. YamamotoK. FukudaT. ShojimaA. NakayamaJ. CarroL. TrujilloM.E. Arthroamide, a cyclic depsipeptide with quorum sensing inhibitory activity from Arthrobacter sp.J. Nat. Prod.201578112827283110.1021/acs.jnatprod.5b00540 26575343
    [Google Scholar]
  35. BusseH.J. Review of the taxonomy of the genus Arthrobacter, emendation of the genus Arthrobacter sensu lato, proposal to reclassify selected species of the genus Arthrobacter in the novel genera Glutamicibacter gen. nov., Paeniglutamicibacter gen. nov., Pseudoglutamicibacter gen. nov., Paenarthrobacter gen. nov. and Pseudarthrobacter gen. nov., and emended description of Arthrobacter roseus. Int. J. Syst. Evol. Microbiol.201666193710.1099/ijsem.0.000702 26486726
    [Google Scholar]
  36. MawlankarR.B. DharneM.S. DastagerS.G. Isolation of potent alpha-glucosidase inhibitor from a novel marine bacterium Arthrobacter enclensis. SN Appl. Sci.20202347410.1007/s42452‑020‑2285‑3
    [Google Scholar]
  37. RamlawiS. AitkenA. AbusharkhS. McMullinD.R. AvisT.J. Arthropeptide A, an antifungal cyclic tetrapeptide from Arthrobacter psychrophenolicus isolated from disease suppressive compost.Nat. Prod. Res.202236225715572310.1080/14786419.2021.2018434 34933636
    [Google Scholar]
  38. MunagantiR.K. MuvvaV. KondaS. NaraganiK. MangamuriU.K. DorigondlaK.R. AkkewarD.M. Antimicrobial profile of Arthrobacter kerguelensis VL-RK_09 isolated from Mango orchards.Braz. J. Microbiol.20164741030103810.1016/j.bjm.2016.07.010 27515463
    [Google Scholar]
  39. KanohK. KohnoS. AsariT. HaradaT. KatadaJ. MuramatsuM. KawashimaH. SekiyaH. UnoI. (−)-Phenylahistin: A new mammalian cell cycle inhibitor produced by aspergillus ustus. Bioorg. Med. Chem. Lett.19977222847285210.1016/S0960‑894X(97)10104‑4
    [Google Scholar]
  40. HayashiY. Yamazaki-NakamuraY. YakushijiF. Medicinal chemistry and chemical biology of diketopiperazine-type antimicrotubule and vascular-disrupting agents.Chem. Pharm. Bull. (Tokyo)201361988990110.1248/cpb.c13‑00404 23995353
    [Google Scholar]
  41. CuiC.B. KakeyaH. OkadaG. OnoseR. OsadaH. Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. I. Taxonomy, fermentation, isolation and biological properties.J. Antibiot. (Tokyo)199649652753310.7164/antibiotics.49.527 8698634
    [Google Scholar]
  42. ZhaoS. SmithK.S. DeveauA.M. DieckhausC.M. JohnsonM.A. MacdonaldT.L. CookJ.M. Biological activity of the tryprostatins and their diastereomers on human carcinoma cell lines.J. Med. Chem.20024581559156210.1021/jm0155953 11931609
    [Google Scholar]
  43. KumarN. MohandasC. NambisanB. KumarD.R.S. LankalapalliR.S. Isolation of proline-based cyclic dipeptides from Bacillus sp. N strain associated with rhabitid entomopathogenic nematode and its antimicrobial properties.World J. Microbiol. Biotechnol.201329235536410.1007/s11274‑012‑1189‑9 23065379
    [Google Scholar]
  44. LiuH. AnM. SiH. ShanY. XuC. HuG. XieY. LiuD. LiS. QiuR. ZhangC. WuY. Identification of cyclic dipeptides and a new compound (6-(5-hydroxy-6-methylheptyl)-5,6-dihydro-2H-pyran-2-one) produced by Streptomyces fungicidicus against Alternaria solani. Molecules20222717564910.3390/molecules27175649 36080412
    [Google Scholar]
  45. WangG. DaiS. ChenM. WuH. XieL. LuoX. LiX. Two diketopiperazine cyclo(pro-phe) isomers from marine bacteria Bacillus subtilis sp. 13-2.Chem. Nat. Compd.201046458358510.1007/s10600‑010‑9680‑8
    [Google Scholar]
  46. FuS. ZhangY. YangC. MengQ. Preparation of uracil by bacteria isolated from Morchella.Pak. J. Pharm. Sci.2020332621625 32276907
    [Google Scholar]
  47. HuangD.Y. NongX.H. ZhangY.Q. XuW. SunL.Y. ZhangT. ChenG.Y. HanC.R. Two new 2,5-diketopiperazine derivatives from mangrove-derived endophytic fungus Nigrospora camelliae-sinensis S30.Nat. Prod. Res.202236143651365610.1080/14786419.2021.1878168 33517796
    [Google Scholar]
  48. StrömK. SjögrenJ. BrobergA. SchnürerJ. Lactobacillus plantarum MiLAB 393 produces the antifungal cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Phe-trans-4-OH-L-Pro) and 3-phenyllactic acid.Appl. Environ. Microbiol.20026894322432710.1128/AEM.68.9.4322‑4327.2002 12200282
    [Google Scholar]
  49. SunS.J. LiuY.C. WengC.H. SunS.W. LiF. LiH. ZhuH. Cyclic dipeptides mediating quorum sensing and their biological effects in hypsizygus marmoreus.Biomolecules202010229810.3390/biom10020298 32070027
    [Google Scholar]
  50. HoldenM.T.G. Ram ChhabraS. De NysR. SteadP. BaintonN.J. HillP.J. ManefieldM. KumarN. LabatteM. EnglandD. RiceS. GivskovM. SalmondG.P.C. StewartG.S.A.B. BycroftB.W. KjellebergS. WilliamsP. Quorum‐sensing cross talk: Isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram‐negative bacteria.Mol. Microbiol.19993361254126610.1046/j.1365‑2958.1999.01577.x 10510239
    [Google Scholar]
  51. LedderhofN.J. CaminitiM.F. BradleyG. LamD.K. Topical 5-fluorouracil is a novel targeted therapy for the keratocystic odontogenic tumor.J. Oral Maxillofac. Surg.201775351452410.1016/j.joms.2016.09.039 27789270
    [Google Scholar]
  52. FanL. PanZ. LiaoX. ZhongY. GuoJ. PangR. ChenX. YeG. SuY. Uracil restores susceptibility of methicillin-resistant Staphylococcus aureus to aminoglycosides through metabolic reprogramming.Front. Pharmacol.202314113368510.3389/fphar.2023.1133685 36762116
    [Google Scholar]
  53. LiuY. YangK. JiaY. ShiJ. TongZ. WangZ. Thymine sensitizes gram-negative pathogens to antibiotic killing.Front. Microbiol.20211262279810.3389/fmicb.2021.622798 33584625
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): Arthrobacter; bioactivity; Cyclic dipeptides; metabolites; soil bacteria; soil sample
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