Unlocking Microbial Potential: Innovations in Natural Product Biosynthesis and Therapeutic Applications

Year : 2025 | Volume : | : | Page : –
By
vector

Nidhul C S,

vector

Navaneeth Gopal,

  1. Student, Department of Bioinformatics, BioNome, Bangalore, Karnataka, India
  2. Student, Department of Bioinformatics, BioNome, Bangalore, Karnataka, India

Abstract document.addEventListener(‘DOMContentLoaded’,function(){frmFrontForm.scrollToID(‘frm_container_abs_130948’);});Edit Abstract & Keyword

MNPs play a pivotal role in diverse fields, spanning medicine, agriculture, and industry. This review paper synthesizes insights from various discussions on microbial natural products, encompassing their sources, bioactive properties, and applications. We explore microbial diversity contributing to natural product synthesis, emphasizing bacteria and fungi as prolific producers. The methods for isolating and characterizing these compounds underscore the interdisciplinary nature of microbial natural product research utilizing various analytical techniques contributing to the structural characterization and dereplication of microbial natural products and enhancing drug discovery processes. Discussions on the potential therapeutic applications reveal antimicrobial, anticancer, and immunomodulatory properties, highlighting the pharmaceutical relevance of these compounds. Additionally, the agricultural and industrial significance of microbial natural products is explored, showcasing their role as biopesticides, biofertilizers, and enzymes in various processes. The importance of databases like NPA and NPBS in advancing MNP research and the complexities of intellectual property and commercialization in the context of patents and licensing is also discussed. The challenges associated with discovering and harnessing microbial natural products, including issues of cultivation and optimization, are also addressed. This abstract provides a comprehensive overview of the multifaceted aspects of microbial natural products, underscoring their significance in scientific, medical, and industrial domains.

Keywords: Biosynthetic Gene Clusters, Methyltransferase , MNPs, Antibacterial , Antifungal

How to cite this article:
Nidhul C S, Navaneeth Gopal. Unlocking Microbial Potential: Innovations in Natural Product Biosynthesis and Therapeutic Applications. International Journal of Fungi. 2025; ():-.
How to cite this URL:
Nidhul C S, Navaneeth Gopal. Unlocking Microbial Potential: Innovations in Natural Product Biosynthesis and Therapeutic Applications. International Journal of Fungi. 2025; ():-. Available from: https://journals.stmjournals.com/ijf/article=2025/view=0

References
document.addEventListener(‘DOMContentLoaded’,function(){frmFrontForm.scrollToID(‘frm_container_ref_130948’);});Edit

  1. Abdel-Razek AS, El-Naggar ME, Allam A, Morsy OM, Othman SI. Microbial natural products in drug discovery. Processes (Basel). 2020;8(4):470. https://doi.org/10.3390/pr8040470
  2. Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79(3):629–61. https://doi.org/10.1021/acs.jnatprod.5b01055
  3. Demain AL. Importance of microbial natural products and the need to revitalize their discovery. J Ind Microbiol Biotechnol. 2014;41(2):185–201. https://doi.org/10.1007/s10295-013-1325-z
  4. 4.Huang T, Lin S. Microbial natural products: A promising source for drug discovery. J Appl Microbiol Biochem. 2017;1(2). https://doi.org/10.21767/2576-1412.100005
  5. 5.Van Middlesworth F, Cannell RJP. Dereplication and partial identification of natural products. In: Natural Products Isolation. Humana Press; 1998. p. 279–327.
  6. 6.Choi H, Oh DC. Considerations of the chemical biology of microbial natural products provide an effective drug discovery strategy. Arch Pharm Res. 2015;38(9):1591–605.    https://doi.org/10.1007/s12272-015-0639-y
  7. 7.Bode HB, Müller R. The impact of bacterial genomics on natural product research. Angew Chem Int Ed Engl. 2005;44(42):6828–46. https://doi.org/10.1002/anie.200501080
  8. 8.Shen B. A new golden age of natural products drug discovery. Cell. 2015;163(6):1297–300. https://doi.org/10.1016/j.cell.2015.11.031
  9. 9.Gupta C. Natural useful therapeutic products from microbes. J Microbiol Exp. 2014;1(1). https://doi.org/10.15406/jmen.2014.01.00006
  10. 10.Dai G, Shen Q, Zhang Y, Bian X. Biosynthesis of fungal natural products involving two separate pathway crosstalk. J Fungi (Basel). 2022;8(3):320. https://doi.org/10.3390/jof8030320
  11. 11.Cox RJ, Gulder TAM. Introduction to engineering the biosynthesis of fungal natural products. Nat Prod Rep. 2023;40(1):7–8. https://doi.org/10.1039/d2np90047e
  12. 12.Wei X, Wang WG, Matsuda Y. Branching and converging pathways in fungal natural product biosynthesis. Fungal Biol Biotechnol. 2022;9(1). https://doi.org/10.1186/s40694-022-00135-w
  13. 13.Yi D, Agarwal V. Biosynthesis-guided discovery and engineering of a-pyrone natural products from type I polyketide synthases. ACS Chem Biol. 2023;18(5):1060–5. https://doi.org/10.1021/acschembio.3c00081
  14. 14.Mitsuhashi T, Barra L, Powers Z, Kojasoy V, Cheng A, Yang F, et al. Exploiting the potential of meroterpenoid cyclases to expand the chemical space of fungal meroterpenoids. Angew Chem Int Ed Engl. 2020;59(52):23772–81. https://doi.org/10.1002/anie.202011171
  15. 15.Thanapipatsiri A, Gomez-Escribano JP, Song L, Bibb MJ, Al-Bassam M, Chandra G, et al. Discovery of unusual biaryl polyketides by activation of a silent Streptomyces venezuelae biosynthetic gene cluster. ChemBioChem. 2016;17(22):2189–98. https://doi.org/10.1002/cbic.201600396
  16. 16.Zhang C, Sultan SA, Rehka, Chen X. Biotechnological applications of S-adenosyl-methionine-dependent methyltransferases for natural products biosynthesis and diversification. Bioresour Bioprocess. 2021;8(1). Available from: https://doi.org/10.1186/s40643-021-00425-y
  17. 17.Rutledge PJ, Challis GL. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol. 2015;13(8):509–23. Available from: https://doi.org/10.1038/nrmicro3496
  18. 18.Obermaier S, Thiele W, Fürtges L, Müller M. Enantioselective phenol coupling by laccases in the biosynthesis of fungal dimeric naphthopyrones. Angew Chem Int Ed Engl. 2019;58(27):9125–8. Available from: https://doi.org/10.1002/anie.201903759
  19. 19.Liu J, Liu A, Hu Y. Enzymatic dimerization in the biosynthetic pathway of microbial natural products. Nat Prod Rep. 2021;38(8):1469–505. Available from: https://doi.org/10.1039/d0np00063a
  20. 20.Sekurova ON, Schneider O, Zotchev SB. Novel bioactive natural products from bacteria via bioprospecting, genome mining, and metabolic engineering. Microb Biotechnol. 2019;12(5):828–44. Available from: https://doi.org/10.1111/1751-7915.13398
  21. 21.Arendt P, Pollier J, Callewaert N, Goossens A. Synthetic biology for production of natural and new-to-nature terpenoids in photosynthetic organisms. Plant J. 2016;87(1):16–37. Available from: https://doi.org/10.1111/tpj.13138
  22. Zhang R. Discovery of new microbial natural products by genome mining. Theor Nat Sci. 2023;3(1):417–23. Available from: https://doi.org/10.54254/2753-8818/3/20220291
  23. 23.Ito T, Masubuchi M. Dereplication of microbial extracts and related analytical technologies. J Antibiot (Tokyo). 2014;67(5):353–60. Available from: https://doi.org/10.1038/ja.2014.12
  24. 24.Caesar LK, Montaser R, Keller NP, Kelleher NL. Metabolomics and genomics in natural products research: complementary tools for targeting new chemical entities. Nat Prod Rep. 2021;38(11):2041–65. Available from: https://doi.org/10.1039/d1np00036e
  25. 25.Albanese D, Donati C. Genome recovery, functional profiling, and taxonomic classification from metagenomes. Methods Mol Biol. 2021;153–72.
  26. 26.Crüsemann M. Coupling mass spectral and genomic information to improve bacterial natural product discovery workflows. Mar Drugs. 2021;19(3):142. Available from: https://doi.org/10.3390/md19030142
  27. 27.Krause J. Applications and restrictions of integrated genomic and metabolomic screening: An accelerator for drug discovery from Actinomycetes? Molecules. 2021;26(18):5450. Available from: https://doi.org/10.3390/molecules26185450
  28. 28.Kuhn S, Nuzillard JM. Easy structural dereplication of natural products by means of predicted carbon-13 nuclear magnetic resonance spectroscopy data. Chem Methods. 2023;3(4). Available from: https://doi.org/10.1002/cmtd.202200054
  29. 29.Gaudêncio SP, Bayram E, Lukic Bilela L, Cueto M, Díaz-Marrero AR, Haznedaroglu BZ, et al. Advanced methods for natural products discovery: Bioactivity screening, dereplication, metabolomics profiling, genomic sequencing, databases and informatic tools, and structure elucidation. Mar Drugs. 2023;21(5):308. Available from: https://doi.org/10.3390/md21050308
  30. 30.Kleks G, Holland DC, Porter J, Carroll AR. Natural products dereplication by diffusion-ordered NMR spectroscopy (DOSY). Chem Sci. 2021;12(32):10930–43. Available from: https://doi.org/10.1039/d1sc02940a
  31. 31.Chávez-Hernández AL, Medina-Franco JL. Natural products subsets: Generation and characterization. Artif Intell Life Sci. 2023;3:100066. Available from: https://doi.org/10.1016/j.ailsci.2023.100066
  32. 32.Qin GF, Zhang X, Zhu F, Huo ZQ, Yao QQ, Feng Q, et al. MS/MS-based molecular networking: An efficient approach for natural products dereplication. Molecules. 2022;28(1):157. Available from: https://doi.org/10.3390/molecules28010157
  33. 33.Flores-Bocanegra L, Al Subeh ZY, Egan JM, El-Elimat T, Raja HA, Burdette JE, et al. Dereplication of fungal metabolites by NMR-based compound networking using MADByTE. J Nat Prod. 2022;85(3):614–24. Available from: https://doi.org/10.1021/acs.jnatprod.1c00841
  34. 34.Nuzillard JM. Taxonomy-focused natural product databases for carbon-13 NMR-based dereplication. Preprints. 2021. Available from: https://doi.org/10.20944/preprints202105.0701.v1
  35. 35.Mohimani H, Gurevich A, Shlemov A, Mikheenko A, Korobeynikov A, Cao L, et al. Dereplication of microbial metabolites through database search of mass spectra. Nat Commun. 2018;9(1). Available from: https://doi.org/10.1038/s41467-018-06082-8
  36. 36.Gao YL, Wang YJ, Chung HH, Chen KC, Shen TL, Hsu CC. Molecular networking as a dereplication strategy for monitoring metabolites of natural product-treated cancer cells. Rapid Commun Mass Spectrom. 2020;34(S1). Available from: https://doi.org/10.1002/rcm.8549
  37. 37.Jenke-Kodama H, Müller R, Dittmann E. Evolutionary mechanisms underlying secondary metabolite diversity. Prog Drug Res. 2007;119–40.
  38. 38.Abdelghani Z, Hourani N, Zaidan Z, Dbaibo G, Mrad M, Hage-Sleiman R. Therapeutic applications and biological activities of bacterial bioactive extracts. Arch Microbiol. 2021;203(8):4755–77. Available from: https://doi.org/10.1007/s00203-021-02505-1
  39. 39.Rahman M, Sarker SD. Antimicrobial natural products. Annu Rep Med Chem. 2020;77–113.
  40. 40.European Centre for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe: annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2018. Publications Office of the European Union; 2019. Available from: https://data.europa.eu/doi/10.2900/22212
  41. 41.Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003;67(4):593–656. Available from: https://doi.org/10.1128/mmbr.67.4.593-656.2003
  42. 42.Li H, Luo YF, Williams BJ, Blackwell TS, Xie CM. Structure and function of OprD protein in Pseudomonas aeruginosa: From antibiotic resistance to novel therapies. Int J Med Microbiol. 2012;302(2):63–8. Available from: https://doi.org/10.1016/j.ijmm.2011.10.001
  43. 43.Vikeli E, Widdick DA, Batey SFD, Heine D, Holmes NA, Bibb MJ, et al. In situ activation and heterologous production of a cryptic lantibiotic from an African plant ant-derived Saccharopolyspora species. Appl Environ Microbiol. 2020;86(3). Available from: https://doi.org/10.1128/aem.01876-19
  44. 44.Dai C, Lin J, Li H, Shen Z, Wang Y, Velkov T, et al. The natural product curcumin as an antibacterial agent: Current achievements and problems. Antioxidants. 2022;11(3):459. Available from: https://doi.org/10.3390/antiox11030459
  45. Darmani H, Smadi EA, Bataineh SM. Blue light emitting diodes enhance the antivirulence effects of Curcumin against Helicobacter pylori. J Med Microbiol. 2020;69(4):617–24. https://doi.org/10.1099/jmm.0.001168
  46. 46.Saraiva RG, Dimopoulos G. Bacterial natural products in the fight against mosquito-transmitted tropical diseases. Nat Prod Rep. 2020;37(3):338–54. https://doi.org/10.1039/c9np00042a
  47. 47.Kardos N, Demain AL. Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl Microbiol Biotechnol. 2011;92(4):677–87. https://doi.org/10.1007/s00253-011-3587-6
  48. 48.Bergeron MG, Brusch JL, Barza M, Weinstein L. Bactericidal activity and pharmacology of cefazolin. Antimicrob Agents Chemother. 1973;4(4):396–401. https://doi.org/10.1128/aac.4.4.396
  49. 49.Levine DP. Vancomycin: A history. Clin Infect Dis. 2006;42(Supplement_1):S5–S12. https://doi.org/10.1086/491709
  50. 50.Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65(2):232–60. https://doi.org/10.1128/mmbr.65.2.232-260.2001
  51. 51.Pongs O. Chloramphenicol. In: Mechanism of Action of Antibacterial Agents. Springer; 1979. p. 26–42.
  52. 52.O’Keeffe J, Doyle S, Kavanagh K. Exposure of the yeast Candida albicans to the anti-neoplastic agent adriamycin increases the tolerance to amphotericin B. J Pharm Pharmacol. 2003;55(12):1629–33. https://doi.org/10.1211/0022357022359
  53. 53.Gupta AK, Tomas E. New antifungal agents. Dermatol Clin. 2003;21(3):565–76. https://doi.org/10.1016/s0733-8635(03)00024-x
  54. 54.Mandell GL, Douglas RG Jr, Bennett JE. Principles and practice of infectious diseases: handbook of antimicrobial therapy 1992. Rev Inst Med Trop Sao Paulo. 1992;34(2):166. https://doi.org/10.1590/s0036-46651992000200018
  55. 55.Instituto de Medicina Tropical de Sao Paulo. Antibiotic study. 1992;34(2):166–6. https://doi.org/10.1590/s0036-46651992000200018
  56. 56.Denning DW. Echinocandins and pneumocandins—a new antifungal class with a novel mode of action. J Antimicrob Chemother. 1997;40(5):611–4. https://doi.org/10.1093/jac/40.5.611
  57. 57.Trookman NS, Rizer RL, Weber T. Treatment of minor wounds from dermatologic procedures: A comparison of three topical wound care ointments using a laser wound model. J Am Acad Dermatol. 2011;64(3 Suppl):S8–15. https://doi.org/10.1016/j.jaad.2010.11.011
  58. 58.Benedict RG, Langlykke AF. Antibiotic activity of Bacillus polymyxa. J Bacteriol. 1947;54(1):24. https://pubmed.ncbi.nlm.nih.gov/20344246/
  59. 59.Falagas ME, Rafailidis PI, Matthaiou DK. Resistance to polymyxins: Mechanisms, frequency and treatment options. Drug Resist Updat. 2010;13(4–5):132–8. https://doi.org/10.1016/j.drup.2010.05.002
  60. 60.Waksman SA, Lechevalier HA. Neomycin, a new antibiotic active against streptomycin-resistant bacteria, including tuberculosis organisms. Science. 1949;109(2830):305–7. https://doi.org/10.1126/science.109.2830.305
  61. 61.Gupte P, Kulkarni B, Ganguli M. Antifungal antibiotics. Appl Microbiol Biotechnol. 2002;58(1):46–57. https://doi.org/10.1007/s002530100822
  62. 62.Mirjalili N, Zormpaidis V, Leadlay PF, Ison AP. The effect of rapeseed oil uptake on the production of erythromycin and triketide lactone by Saccharopolyspora erythraea. Biotechnol Prog. 1999;15(5):911–8. https://doi.org/10.1021/bp990099h
  63. 63.Sensi P. History of the development of rifampin. Clin Infect Dis. 1983;5(Suppl 3):S402–6. https://doi.org/10.1093/clinids/5.supplement_3.s402
  64. 64.Fischer J, Ganellin CR. Analogue-based drug discovery. John Wiley & Sons; 2006.
  65. 65.Pogliano J, Pogliano N, Silverman JA. Daptomycin-mediated reorganization of membrane architecture causes mislocalization of essential cell division proteins. J Bacteriol. 2012;194(17):4494–504. https://doi.org/10.1128/jb.00011-12
  66. 66.Guay DR. Daptomycin: The first approved lipopeptide antimicrobial. Consult Pharm. 2004;19(7):614–28. https://doi.org/10.4140/tcp.n.2004.614
  67. 67.Martens E, Demain AL. Platensimycin and platencin: Promising antibiotics for future application in human medicine. J Antibiot. 2011;64(11):705–10. https://doi.org/10.1038/ja.2011.80
  68. 68.Arqués JL, Rodríguez E, Nuñez M, Medina M. Antimicrobial activity of Nisin, reuterin, and the lactoperoxidase system on Listeria monocytogenes and Staphylococcus aureus in Cuajada, a semisolid dairy product manufactured in Spain. J Dairy Sci. 2008;91(1):70–5. https://doi.org/10.3168/jds.2007-0133
  69. 69.Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, et al. A new antibiotic kills pathogens without detectable resistance. Nature. 2015;517(7535):455–9. https://doi.org/10.1038/nature14098
  70. 70.Zaher AM, Makboul MA, Moharram AM, Tekwani BL, Calderón AI. A new enniatin antibiotic from the endophyte Fusarium tricinctum Corda. J Antibiot. 2015;68(3):197–200. https://doi.org/10.1038/ja.2014.129
  71. 71.Essig A, Hofmann D, Münch D, Gayathri S, Künzler M, Kallio PT, et al. Copsin, a novel peptide-based fungal antibiotic interfering with the peptidoglycan synthesis. J Biol Chem. 2014;289(50):34953–64. https://doi.org/10.1074/jbc.m114.599878
  72. 72.Cociancich S, Pesic A, Petras D, Uhlmann S, Kretz J, Schubert V, et al. The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine. Nat Chem Biol. 2015;11(3):195–7. https://doi.org/10.1038/nchembio.1734
  73. Baumann S, Herrmann J, Raju R, Steinmetz H, Mohr KI, Hüttel S, et al. Cystobactamids: Myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity. Angew Chem Int Ed Engl. 2014;53(52):14605–9. https://doi.org/10.1002/anie.201409964
  74. 74.Frediansyah A, Sofyantoro F, Alhumaid S, Al Mutair A, Albayat HI, Altaweil HI, et al. Microbial natural products with antiviral activities, including anti-SARS-CoV-2: A review. Molecules. 2022;27(13):4305. https://doi.org/10.3390/molecules27134305
  75. 75.Augostine CR, Avery SV. Discovery of natural products with antifungal potential through combinatorial synergy. Front Microbiol. 2022;13. https://doi.org/10.3389/fmicb.2022.866840
  76. 76.Composition having inhibitory effect on virus and bacteria. Justia.com. Retrieved January 4, 2024. https://patents.justia.com/patent/11666621
  77. 77.Mahoney M, Damalanka VC, Tartell MA, Chung DH, Lourenço AL, Pwee D, et al. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. Proc Natl Acad Sci USA. 2021;118(43). https://doi.org/10.1073/pnas.2108728118
  78. 78.Férir G, Petrova MI, Andrei G, Huskens D, Hoorelbeke B, Snoeck R, et al. The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. PLoS One. 2013;8(5):e64010. https://doi.org/10.1371/journal.pone.0064010
  79. 79.ElNaggar MH, Abdelwahab GM, Kutkat O, GabAllah M, Ali MA, El-Metwally MEA, et al. Aurasperone A inhibits SARS CoV-2 in vitro: An integrated in vitro and in silico study. Mar Drugs. 2022;20(3):179. https://doi.org/10.3390/md20030179
  80. 80.Nakajima S, Watashi K, Ohashi H, Kamisuki S, Izaguirre-Carbonell J, Kwon AT-J, et al. Fungus-derived neoechinulin B as a novel antagonist of liver X receptor, identified by chemical genetics using a hepatitis C virus cell culture system. J Virol. 2016;90(20):9058–74. https://doi.org/10.1128/jvi.00856-16
  81. 81.Zhao Y, Liu D, Proksch P, Zhou D, Lin W. Truncateols O-V, further isoprenylated cyclohexanols from the sponge-associated fungus Truncatella angustata with antiviral activities. Phytochemistry. 2018;155:61–8. https://doi.org/10.1016/j.phytochem.2018.07.017
  82. 82.Agarwal AK, Xu T, Jacob MR, Feng Q, Lorenz MC, Walker LA, et al. Role of heme in the antifungal activity of the azaoxoaporphine alkaloid sampangine. Eukaryot Cell. 2008;7(2):387–400. https://doi.org/10.1128/ec.00323-07
  83. 83.Michalak EM, Burr ML, Bannister AJ, Dawson MA. The roles of DNA, RNA and histone methylation in ageing and cancer. Nat Rev Mol Cell Biol. 2019;20(10):573–89. https://doi.org/10.1038/s41580-019-0143-1
  84. 84.Valentová J, Lintnerová L, Miklášová N, Obonová B, Habala L. Analogues of anticancer natural products: Chiral aspects. Int J Mol Sci. 2023;24(6):5679. https://doi.org/10.3390/ijms24065679
  85. 85.Zhang X, Ye X, Chai W, Lian XY, Zhang Z. New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338. Mar Drugs. 2016;14(10):181. https://doi.org/10.3390/md14100181
  86. 86.Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204–18. https://doi.org/10.18632/oncotarget.23208
  87. 87.Bi YL, Mi PY, Zhao SJ, Pan HM, Li HJ, Liu F, et al. Salinomycin exhibits anti-angiogenic activity against human glioma in vitro and in vivo by suppressing the VEGF-VEGFR2-AKT/FAK signaling axis. Int J Mol Med. 2017;39(5):1255–61. https://doi.org/10.3892/ijmm.2017.2940
  88. 88.Itoh T, Kinoshita M, Aoki S, Kobayashi M. Komodoquinone A, a novel neuritogenic anthracycline, from marine Streptomyces sp. KS3. J Nat Prod. 2003;66(10):1373–7. https://doi.org/10.1021/np030212k
  89. 89.Dhaneesha M, Benjamin Naman C, Krishnan KP, Sinha RK, Jayesh P, Joseph V, et al. Streptomyces artemisiae MCCB 248 isolated from Arctic fjord sediments has unique PKS and NRPS biosynthetic genes and produces potential new anticancer natural products. 3 Biotech. 2017;7(1). https://doi.org/10.1007/s13205-017-0610-3
  90. 90.Liu L, Zhu H, Wu W, Shen Y, Lin X, Wu Y, et al. Neoantimycin F, a Streptomyces-derived natural product induces mitochondria-related apoptotic death in human non-small cell lung cancer cells. Front Pharmacol. 2019;10. https://doi.org/10.3389/fphar.2019.01042
  91. 91.Hu Y, Martinez ED, MacMillan JB. Anthraquinones from a marine-derived Streptomyces spinoverrucosus. J Nat Prod. 2012;75(10):1759–64. https://doi.org/10.1021/np3004326
  92. 92.Balachandran C, Sangeetha B, Duraipandiyan V, Raj MK, Ignacimuthu S, Al-Dhabi NA, et al. A flavonoid isolated from Streptomyces sp. (ERINLG-4) induces apoptosis in human lung cancer A549 cells through p53 and cytochrome c release caspase dependant pathway. Chem Biol Interact. 2014;224:24–35. https://doi.org/10.1016/j.cbi.2014.09.019
  93. 93.Choi YK, Kim J, Lee KM, Choi YJ, Ye BR, Kim MS, et al. Tuberatolide B suppresses cancer progression by promoting ROS-mediated inhibition of STAT3 signaling. Mar Drugs. 2017;15(3):55. https://doi.org/10.3390/md15030055
  94. 94.Bahrami A, Hasanzadeh M, Hassanian SM, ShahidSales S, Ghayour-Mobarhan M, Ferns GA, et al. The potential value of the PI3K/Akt/mTOR signaling pathway for assessing prognosis in cervical cancer and as a target for therapy. J Cell Biochem. 2017;118(12):4163–9. https://doi.org/10.1002/jcb.26118
  95. 95.Zhang W, Che Q, Tan H, Qi X, Li J, Li D, et al. Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system. Sci Rep. 2017;7(1). https://doi.org/10.1038/srep42180
  96. 96.Dan VM, Muralikrishnan B, Sanawar R, Vinodh B, Burkul BB, Srinivas KP, et al. Streptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines. Sci Rep. 2018;8(1). https://doi.org/10.1038/s41598-018-21249-5
  97. 97.Gorska M. Geldanamycin and its derivatives as Hsp90 inhibitors. Front Biosci. 2012;17(7):2269. https://doi.org/10.2741/4050
  98. 98.Kanimozhi G, Prasad NR. Anticancer effect of caffeic acid on human cervical cancer cells. In: Coffee in Health and Disease Prevention. Elsevier; 2015. p. 655–61.
  99. 99.Yin J, Dong Q, Zheng M, Xu X, Zou G, Ma G, et al. Antitumor activity of dobutamine on human osteosarcoma cells. Oncol Lett. 2016;11(6):3676–80. https://doi.org/10.3892/ol.2016.4479
  100. 100.Fatourachi P, Faramarziyan Azimi Maragheh B, Mohammadi SM, Valipour B, Dehnad A, Nozad Charoudeh H. Extracted metabolite from Streptomyces Levis ABRIINW111 altered the gene expression in colon cancer. Gastroenterol Hepatol Bed Bench. 2018;11(1):34–41.
  101. 101.Tan LTH, Chan KG, Pusparajah P, Yin WF, Khan TM, Lee LH, et al. Mangrove derived Streptomyces sp. MUM265 as a potential source of antioxidant and anticolon-cancer agents. BMC Microbiol. 2019;19(1). https://doi.org/10.1186/s12866-019-1409-7
  102. 102.Jeong SY, Han MH, Jin CY, Kim GY, Choi BT, Nam TJ, et al. Apoptosis induction of human leukemia cells by Streptomyces sp. SY-103 metabolites through activation of caspase-3 and inactivation of Akt. Int J Mol Med. 2010;25(1):31–40.
  103. 103.Valipour B, Mohammadi SM, Abedelahi A, Faramarzian Azimi Maragheh B, Naderali E, Dehnad A, et al. Culture filtrate ether extracted metabolites from Streptomyces levis ABRIINW111 increased apoptosis and reduced proliferation in acute lymphoblastic leukemia. Biomed Pharmacother. 2018;108:216–23. https://doi.org/10.1016/j.biopha.2018.09.050
  104. 104.Plitzko B, Kaweesa EN, Loesgen S. The natural product mensacarcin induces mitochondrial toxicity and apoptosis in melanoma cells. J Biol Chem. 2017;292(51):21102–16. https://doi.org/10.1074/jbc.m116.774836
  105. Rambabu V, Suba S, Vijayakumar S. Antimicrobial and antiproliferative prospective of kosinostatin – a secondary metabolite isolated from Streptomyces sp. J Pharm Anal. 2015;5(6):378–82. https://doi.org/10.1016/j.jpha.2014.11.002
  106. 106.Safarpour A, Ebrahimi M, Shahzadeh Fazeli SA, Amoozegar MA. Supernatant metabolites from halophilic Archaea to reduce tumorigenesis in prostate cancer in-vitro and in-vivo. Iran J Pharm Res. 2019;18(1):241–53.
  107. 107.Donnelly A, Blagg B. Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket. Curr Med Chem. 2008;15(26):2702–17. https://doi.org/10.2174/092986708786242895
  108. 108.Krishnaiah D, Sarbatly R, Nithyanandam R. A review of the antioxidant potential of medicinal plant species. Food Bioprod Process. 2011;89(3):217–33. doi:10.1016/j.fbp.2010.04.008
  109. 109.Naqvi SR, Nadeem S, Komal S, Naqvi SA, Mubarik MS, Qureshi SY, et al. Antioxidants: Natural Antibiotics. In: Shalaby E, editor. Antioxidants. IntechOpen; 2019.
  110. 110.Wu T, Zang X, He M, Pan S, Xu X. Structure-activity relationship of flavonoids on their anti-Escherichia coli activity and inhibition of DNA gyrase. J Agric Food Chem. 2013;61(34):8185–90. doi:10.1021/jf402222v
  111. 111.Plaper A, Golob M, Hafner I, Oblak M, Solmajer T, Jerala R. Characterization of quercetin binding site on DNA gyrase. Biochem Biophys Res Commun. 2003;306(2):530–6. doi:10.1016/s0006-291x(03)01006-4
  112. 112.Gradišar H, Pristovšek P, Plaper A, Jerala R. Green tea catechins inhibit bacterial DNA gyrase by interaction with its ATP binding site. J Med Chem. 2007;50(2):264–71. doi:10.1021/jm060817o
  113. 113.Wang Q, Wang H, Xie M. Antibacterial mechanism of soybean isoflavone on Staphylococcus aureus. Arch Microbiol. 2010;192(11):893–8. doi:10.1007/s00203-010-0617-1
  114. 114.Ulanowska K, Tkaczyk A, Konopa G, Wegrzyn G. Differential antibacterial activity of genistein arising from global inhibition of DNA, RNA and protein synthesis in some bacterial strains. Arch Microbiol. 2006;184(5):271–8. doi:10.1007/s00203-005-0063-7
  115. 115.Tsuchiya H, Iinuma M. Reduction of membrane fluidity by antibacterial sophoraflavanone G isolated from Sophora exigua. Phytomedicine. 2000;7(2):161–5. doi:10.1016/s0944-7113(00)80089-6
  116. 116.Tsuchiya H, Sato M, Miyazaki T, Fujiwara S, Tanigaki S, Ohyama M, et al. Comparative study on the antibacterial activity of phytochemical flavanones against methicillin-resistant Staphylococcus aureus. J Ethnopharmacol. 1996;50(1):27–34. doi:10.1016/0378-8741(96)85514-0
  117. 117.Shan B, Cai YZ, Brooks JD, Corke H. The in vitro antibacterial activity of dietary spice and medicinal herb extracts. Int J Food Microbiol. 2007;117(1):112–9. doi:10.1016/j.ijfoodmicro.2007.03.003
  118. 118.Ikigai H, Nakae T, Hara Y, Shimamura T. Bactericidal catechins damage the lipid bilayer. Biochim Biophys Acta Biomembr. 1993;1147(1):132–6. doi:10.1016/0005-2736(93)90323-r
  119. 119.Borges A, Ferreira C, Saavedra MJ, Simões M. Antibacterial activity and mode of action of ferulic and gallic acids against pathogenic bacteria. Microb Drug Resist. 2013;19(4):256–65. doi:10.1089/mdr.2012.0244
  120. 120.Cushnie TP, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005;26(5):343–56. doi:10.1016/j.ijantimicag.2005.09.002
  121. 121.Singh B, Mohanty D, Bakshi V, Gujjar RS, Upadhyay AK. The distinction of omics in amelioration of food crops nutritional value. In: Bioinformatics for agriculture: High-throughput approaches. Springer Singapore; 2021. p. 85–99.
  122. 122.Molyneux RJ. Research opportunities for bioactive natural constituents in agriculture and food prepared for the 50th anniversary of the journal of agricultural and food chemistry. J Agric Food Chem. 2002;50(24):6939–42. doi:10.1021/jf0207068
  123. 123.Routray W, Orsat V. Agricultural and food industry by-products: Source of bioactive components for functional beverages. In: Grumezescu AM, Holban AM, editors. Nutrients in Beverages. Elsevier; 2019. p. 543–589.
  124. Ivanov K, Ivanova S, Georgieva M, Atanasov P. Production and regulatory analytical control of amino acids include in food additives. Pharmacia. 2014;61(2):48–54.
  125. 125.Mahmood ZA. Microbial amino acids production. In: Microbial biotechnology, progress and trends. Vol. Chapter 9. CRC Press; 2015.
  126. 126.Demain AL. Reviews: The business of biotechnology. Ind Biotechnol (N Rochelle N Y). 2007;3(3):269–83. https://doi.org/10.1089/ind.2007.3.269
  127. 127.Mata-Gómez LC, Montañez JC, Méndez-Zavala A, Aguilar CN. Biotechnological production of carotenoids by yeasts: an overview. Microb Cell Fact. 2014;13(1):12. https://doi.org/10.1186/1475-2859-13-12
  128. 128.Adrio JL, Demain AL. Microbial enzymes: tools for biotechnological processes. Biomolecules. 2014;4(1):117–39. https://doi.org/10.3390/biom4010117
  129. 129.Max B, Salgado JM, Rodríguez N, Cortés S, Converti A, Domínguez JM. Biotechnological production of citric acid. Braz J Microbiol. 2010;41(4):862–75. https://doi.org/10.1590/S1517-83822010000400005
  130. 130.Otten A, Brocker M, Bott M. Metabolic engineering of Corynebacterium glutamicum for the production of itaconate. Metab Eng. 2015;30:156–65. https://doi.org/10.1016/j.ymben.2015.06.003
  131. 131.Martinez F, Balciunas EM, Salgado JM. Lactic acid properties, applications and production:    a review. Trends Food Sci Technol. 2013;30:70–83.
  132. 132.Wang ZX, Zhuge J, Fang H, Prior BA. Glycerol production by microbial fermentation: a review. Biotechnol Adv. 2001;19(3):201–23. https://doi.org/10.1016/s0734-9750(01)00060-x
  133. Sarris D, Papanikolaou S. Biotechnological production of ethanol: Biochemistry, processes and technologies. Eng Life Sci. 2016;16(4):307–29. https://doi.org/10.1002/elsc.201400199
  134. 134.Canan U. Microorganisms in biological pest control—a review (bacterial toxin application and effect of environmental factors). In: Silva-Opps M, editor. Current progress in biological research. InTech; 2013.
  135. 135.Van Santen JA, Poynton EF, Iskakova D, McMann E, Alsup TA, Clark TN, et al. The Natural Products Atlas 2.0: a database of microbially-derived natural products. Nucleic Acids Res. 2022;50(D1):D1317–23. https://doi.org/10.1093/nar/gkab941
  136. 136.Van Santen JA, Kautsar SA, Medema MH, Linington RG. Microbial natural product databases: moving forward in the multi-omics era. Nat Prod Rep. 2021;38(1):264–78. https://doi.org/10.1039/d0np00053a
  137. 137.Zhao H, Yang Y, Wang S, Yang X, Zhou K, Xu C, et al. NPASS database update 2023: quantitative natural product activity and species source database for biomedical research. Nucleic Acids Res. 2023;51(D1):D621–8. https://doi.org/10.1093/nar/gkac1069
  138. 138.Moumbock AFA, Gao M, Qaseem A, Li J, Kirchner PA, Ndingkokhar B, et al. StreptomeDB 3.0: an updated compendium of streptomycetes natural products. Nucleic Acids Res. 2021;49(D1):D600–4. https://doi.org/10.1093/nar/gkaa868
  139. 139.Chassagne F, Cabanac G, Hubert G, David B, Marti G. The landscape of natural product diversity and their pharmacological relevance from a focus on the Dictionary of Natural Products®. Phytochem Rev. 2019;18(3):601–22. https://doi.org/10.1007/s11101-019-09606-2
  140. 140.Katz E, Mauger AB. Dictionary of Antibiotics and Related Substances. Edited by Bycroft BW. Chapman and Hall: London; 1988. J Pharm Sci. 1990;79(2):187. https://doi.org/10.1002/jps.2600790222
  141. 141.Conway KR, Boddy CN. ClusterMine360: a database of microbial PKS/NRPS biosynthesis. Nucleic Acids Res. 2012;41(D1):D402–7. https://doi.org/10.1093/nar/gks993
  142. 142.Ichikawa N, Sasagawa M, Yamamoto M, Komaki H, Yoshida Y, Yamazaki S, et al. DoBISCUIT: a database of secondary metabolite biosynthetic gene clusters. Nucleic Acids Res. 2013;41(Database issue):D408–14. https://doi.org/10.1093/nar/gks1177
  143. 143.Terlouw BR, Blin K, Navarro-Muñoz JC, Avalon NE, Chevrette MG, Egbert S, et al. MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters. Nucleic Acids Res. 2023;51(D1):D603–10. https://doi.org/10.1093/nar/gkac1049
  144. 144.Palaniappan K, Chen I-MA, Chu K, Ratner A, Seshadri R, Kyrpides NC, et al. IMG-ABC v.5.0: An update to the IMG/atlas of biosynthetic gene clusters knowledgebase. Nucleic Acids Res. 2019. https://doi.org/10.1093/nar/gkz932
  145. 145.Blin K, Shaw S, Medema MH, Weber T. The antiSMASH database version 4: additional genomes and BGCs, new sequence-based searches and more. Nucleic Acids Res. 2024;52(D1):D586–9. https://doi.org/10.1093/nar/gkad984
  146. 146.Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol. 2016;34(8):828–37. https://doi.org/10.1038/nbt.3597
  147. 147.Yurekten O, Payne T, Tejera N, Amaladoss FX, Martin C, Williams M, et al. MetaboLights: open data repository for metabolomics. Nucleic Acids Res. 2024;52(D1):D640–6. https://doi.org/10.1093/nar/gkad1045
  148. 148.Puzzling out the patent-eligibility of natural products. Finnegan | Leading IP+ Law Firm [Internet]. [cited 2024 Jan 4]. Available from: https://www.finnegan.com/en/insights/articles/puzzling-out-the-patent-eligibility-of-natural-products.html
  149. 149.Ganguli P. Intellectual property rights: mothering innovations to markets. World Pat Inf. 2000;22(1–2):43–52. https://doi.org/10.1016/s0172-2190(00)00029-6
  150. 150.Boyd MR. The position of intellectual property rights in drug discovery and development from natural products. J Ethnopharmacol. 1996;51(1–3):17–27. https://doi.org/10.1016/0378-8741(95)01346-6
  151. 151.Chong LK, Udell LJ, Downs BW. Regulatory approvals, intellectual property, branding and trademark in nutraceuticals and functional foods. In: Developing New Functional Food and Nutraceutical Products. Elsevier; 2017. p. 417–28.
  152. 152.Luo L, Yang J, Wang C, Wu J, Li Y, Zhang X, et al. Natural products for infectious microbes and diseases: an overview of sources, compounds, and chemical diversities. Sci China Life Sci. 2022;65(6):1123–45. https://doi.org/10.1007/s11427-020-1959-5
  153. 153.Deane CD, Mitchell DA. Lessons learned from the transformation of natural product discovery to a genome-driven endeavor. J Ind Microbiol Biotechnol. 2014;41(2):315–31. https://doi.org/10.1007/s10295-013-1361-8
  154. 154.Basmadjian C, Zhao Q, Bentouhami E, Djehal A, Nebigil CG, Johnson RA, et al. Cancer wars: natural products strike back. Front Chem. 2014;2:20. https://doi.org/10.3389/fchem.2014.00020
  155. 155.Mishra B, Varjani S, Kumar G, Awasthi MK, Awasthi SK, Sindhu R, et al. Microbial approaches for remediation of pollutants: Innovations, future outlook, and challenges. Energy Environ. 2021;32(6):1029–58. https://doi.org/10.1177/0958305×19896781
  156. 156.eon J-G, Rosalen PL, Falsetta ML, Koo H. Natural products in caries research: Current (limited) knowledge, challenges and future perspective. Caries Res. 2011;45(3):243–63. https://doi.org/10.1159/000327250
  157. 157.Bhardwaj S, Verma R, Gupta J. Challenges and future prospects of herbal medicine. Int Res   Med Health Sci. 2018. https://doi.org/10.36437/irmhs.2018.1.1.d

Ahead of Print Subscription Review Article
Volume
Received 28/12/2024
Accepted 30/12/2024
Published 03/01/2025