Skip to main content
SpringerLink
Log in

Advances in microbial culturing conditions to activate silent biosynthetic gene clusters for novel metabolite production

  • Natural Products - Mini Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Natural products (NPs) produced by bacteria and fungi are often used as therapeutic agents due to their complex structures and wide range of bioactivities. Enzymes that build NPs are encoded by co-localized biosynthetic gene clusters (BGCs), and genome sequencing has recently revealed that many BGCs are “silent” under standard laboratory conditions. There are numerous methods used to activate “silent” BGCs that rely either upon altering culture conditions or genetic modification. In this review, we discuss several recent microbial cultivation methods that have been used to expand the scope of NPs accessible in the laboratory. These approaches are divided into three categories: addition of a physical scaffold, addition of small molecule elicitors, and co-cultivation with another microbe.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17

Similar content being viewed by others

References

  1. Afiyatullov SS, Zhuravleva OI, Antonov AS et al (2018) Prenylated indole alkaloids from co-culture of marine-derived fungi Aspergillus sulphureus and Isaria felina. J Antibiot 71:846–853. https://doi.org/10.1038/s41429-018-0072-9

    Article  CAS  PubMed  Google Scholar 

  2. Akhter N, Liu Y, Auckloo BN et al (2018) Stress-driven discovery of new angucycline-type antibiotics from a marine Streptomyces pratensis NA-ZhouS1. Mar Drugs 16:331. https://doi.org/10.3390/md16090331

    Article  CAS  PubMed Central  Google Scholar 

  3. Akone SH, Mándi A, Kurtán T et al (2016) Inducing secondary metabolite production by the endophytic fungus Chaetomium sp. through fungal–bacterial co-culture and epigenetic modification. Tetrahedron 72:6340–6347. https://doi.org/10.1016/j.tet.2016.08.022

    Article  CAS  Google Scholar 

  4. Alonso S, Rendueles M, Díaz M (2017) Tunable decoupled overproduction of lactobionic acid in Pseudomonas taetrolens through temperature-control strategies. Process Biochem 58:9–16. https://doi.org/10.1016/j.procbio.2017.04.034

    Article  CAS  Google Scholar 

  5. Ancheeva E, Mándi A, Király SB et al (2018) Chaetolines A and B, Pyrano[3,2-f]isoquinoline alkaloids from cultivation of Chaetomium sp. in the presence of autoclaved Pseudomonas aeruginosa. J Nat Prod 81:2392–2398. https://doi.org/10.1021/acs.jnatprod.8b00373

    Article  CAS  PubMed  Google Scholar 

  6. Ancheeva E, Küppers L, Akone SH et al (2017) Expanding the metabolic profile of the fungus Chaetomium sp. through co-culture with autoclaved Pseudomonas aeruginosa. Eur J Org Chem 2017:3256–3264. https://doi.org/10.1002/ejoc.201700288

    Article  CAS  Google Scholar 

  7. Anjum K, Sadiq I, Chen L et al (2018) Novel antifungal janthinopolyenemycins A and B from a co-culture of marine-associated Janthinobacterium spp. ZZ145 and ZZ148. Tetrahedron Lett 59:3490–3494. https://doi.org/10.1016/j.tetlet.2018.08.022

    Article  CAS  Google Scholar 

  8. Auckloo BN, Pan C, Akhter N et al (2017) Stress-driven discovery of novel cryptic antibiotics from a marine fungus Penicillium sp. BB1122. Front Microbiol 8:1450. https://doi.org/10.3389/fmicb.2017.01450

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bai J, Mu R, Dou M et al (2018) Epigenetic modification in histone deacetylase deletion strain of Calcarisporium arbuscula leads to diverse diterpenoids. Acta Pharm Sin B 8:687–697. https://doi.org/10.1016/j.apsb.2017.12.012

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ballouz S, Francis AR, Lan R, Tanaka MM (2010) Conditions for the evolution of gene clusters in bacterial genomes. PLoS Comput Biol 6:e1000672. https://doi.org/10.1371/journal.pcbi.1000672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Baltz RH (2017) Gifted microbes for genome mining and natural product discovery. J Ind Microbiol Biotechnol 44:573–588. https://doi.org/10.1007/s10295-016-1815-x

    Article  CAS  PubMed  Google Scholar 

  12. Barnhart MM, Lynem J, Chapman MR (2006) GlcNAc-6P levels modulate the expression of Curli fibers by Escherichia coli. J Bacteriol 188:5212–5219. https://doi.org/10.1128/JB.00234-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Biggins JB, Ternei MA, Brady SF (2012) Malleilactone, a polyketide synthase-derived virulence factor encoded by the cryptic secondary metabolome of Burkholderia pseudomallei group pathogens. J Am Chem Soc 134:13192–13195. https://doi.org/10.1021/ja3052156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Boffa LC, Vidali G, Mann RS, Allfrey VG (1978) Suppression of histone deacetylation in vivo and in vitro by sodium butyrate. J Biol Chem 253:3364–3366

    CAS  PubMed  Google Scholar 

  15. Boruta T, Bizukojc M (2019) Application of aluminum oxide nanoparticles in Aspergillus terreus cultivations: evaluating the effects on lovastatin production and fungal morphology. Biomed Res Int 2019:1–11. https://doi.org/10.1155/2019/5832496

    Article  CAS  Google Scholar 

  16. Bosello M, Zeyadi M, Kraas FI et al (2013) Structural Characterization of the heterobactin siderophores from Rhodococcus erythropolis PR4 and elucidation of their biosynthetic machinery. J Nat Prod 76:2282–2290. https://doi.org/10.1021/np4006579

    Article  CAS  PubMed  Google Scholar 

  17. Brinkmann C, Kearns P, Evans-Illidge E, Kurtbӧke D (2017) Diversity and bioactivity of marine bacteria associated with the sponges Candidaspongia flabellata and Rhopaloeides odorabile from the Great Barrier Reef in Australia. Diversity 9:39. https://doi.org/10.3390/d9030039

    Article  CAS  Google Scholar 

  18. Craney A, Ozimok C, Pimentel-Elardo SM et al (2012) Chemical perturbation of secondary metabolism demonstrates important links to primary metabolism. Chem Biol 19:1020–1027. https://doi.org/10.1016/j.chembiol.2012.06.013

    Article  CAS  PubMed  Google Scholar 

  19. Dashti Y, Grkovic T, Abdelmohsen UR et al (2017) Actinomycete metabolome induction/suppression with N-acetylglucosamine. J Nat Prod 80:828–836. https://doi.org/10.1021/acs.jnatprod.6b00673

    Article  CAS  PubMed  Google Scholar 

  20. Davie JR (2003) Inhibition of histone deacetylase activity by butyrate. J Nutr 133:2485S–2493S. https://doi.org/10.1093/jn/133.7.2485S

    Article  CAS  PubMed  Google Scholar 

  21. Davies J, Spiegelman GB, Yim G (2006) The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol 9:445–453. https://doi.org/10.1016/j.mib.2006.08.006

    Article  CAS  PubMed  Google Scholar 

  22. de Oca-Mejía MM, Castillo-Juárez I, Martínez-Vázquez M et al (2015) Influence of quorum sensing in multiple phenotypes of the bacterial pathogen Chromobacterium violaceum. Pathog Dis 73:1–4. https://doi.org/10.1093/femspd/ftu019

    Article  CAS  PubMed  Google Scholar 

  23. Du C, van Wezel GP (2018) Mining for microbial gems: integrating proteomics in the postgenomic natural product discovery pipeline. Proteomics 18:1700332. https://doi.org/10.1002/pmic.201700332

    Article  CAS  PubMed Central  Google Scholar 

  24. El-Hawary SS, Sayed AM, Mohammed R et al (2018) New Pim-1 kinase inhibitor from the co-culture of two sponge-associated Actinomycetes. Front Chem 6:538. https://doi.org/10.3389/fchem.2018.00538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Everest GJ, Meyers PR (2011) Evaluation of the antibiotic biosynthetic potential of the genus Amycolatopsis and description of Amycolatopsis circi sp. nov., Amycolatopsis equina sp. nov. and Amycolatopsis hippodromi sp. nov. J Appl Microbiol 111:300–311. https://doi.org/10.1111/j.1365-2672.2011.05058.x

    Article  CAS  PubMed  Google Scholar 

  26. Feng X, He C, Jiao L et al (2019) Analysis of differential expression proteins reveals the key pathway in response to heat stress in Alicyclobacillus acidoterrestris DSM 3922T. Food Microbiol 80:77–84. https://doi.org/10.1016/j.fm.2019.01.003

    Article  CAS  PubMed  Google Scholar 

  27. Gilmore SA, Naseem S, Konopka JB, Sil A (2013) N-Acetylglucosamine (GlcNAc) triggers a rapid, temperature-responsive morphogenetic program in thermally dimorphic fungi. PLoS Genet. https://doi.org/10.1371/journal.pgen.1003799

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gonciarz J, Bizukojc M (2014) Adding talc microparticles to Aspergillus terreus ATCC 20542 preculture decreases fungal pellet size and improves lovastatin production. Eng Life Sci 14:190–200. https://doi.org/10.1002/elsc.201300055

    Article  CAS  Google Scholar 

  29. Hegemann JD, Zimmermann M, Xie X, Marahiel MA (2015) Lasso peptides: an intriguing class of bacterial natural products. Acc Chem Res 48:1909–1919. https://doi.org/10.1021/acs.accounts.5b00156

    Article  CAS  PubMed  Google Scholar 

  30. Jiang J, Sun Y-F, Tang X et al (2018) Alkaline pH shock enhanced production of validamycin A in fermentation of Streptomyces hygroscopicus. Bioresour Technol 249:234–240. https://doi.org/10.1016/j.biortech.2017.10.012

    Article  CAS  PubMed  Google Scholar 

  31. Ju K-S, Zhang X, Elliot MA (2017) New kid on the block: LmbU expands the repertoire of specialized metabolic regulators in Streptomyces. J Bacteriol. https://doi.org/10.1128/JB.00559-17

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kawai K, Wang G, Okamoto S, Ochi K (2007) The rare earth, scandium, causes antibiotic overproduction in Streptomyces spp. FEMS Microbiol Lett 274:311–315. https://doi.org/10.1111/j.1574-6968.2007.00846.x

    Article  CAS  PubMed  Google Scholar 

  33. Keilhofer N, Nachtigall J, Kulik A et al (2018) Streptomyces AcH 505 triggers production of a salicylic acid analogue in the fungal pathogen Heterobasidion abietinum that enhances infection of Norway spruce seedlings. Antonie Van Leeuwenhoek 111:691–704. https://doi.org/10.1007/s10482-018-1017-9

    Article  CAS  PubMed  Google Scholar 

  34. Kharel MK, Pahari P, Shepherd MD et al (2012) Angucyclines: biosynthesis, mode-of-action, new natural products, and synthesis. Nat Prod Rep 29:264–325. https://doi.org/10.1039/c1np00068c

    Article  CAS  PubMed  Google Scholar 

  35. Kim SD, Park SK, Cho JY et al (2006) Surfactin C inhibits platelet aggregation. J Pharm Pharmacol 58:867–870. https://doi.org/10.1211/jpp.58.6.0018

    Article  CAS  PubMed  Google Scholar 

  36. Lehmann LH, Jebessa ZH, Kreusser MM et al (2018) A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway. Nat Med 24:62–72. https://doi.org/10.1038/nm.4452

    Article  CAS  PubMed  Google Scholar 

  37. Ligon BL (2004) Penicillin: its discovery and early development. Semin Pediatr Infect Dis 15:52–57. https://doi.org/10.1053/j.spid.2004.02.001

    Article  PubMed  Google Scholar 

  38. Luger K, Richmond TJ (1998) The histone tails of the nucleosome. Curr Opin Genet Dev 8:140–146

    Article  CAS  Google Scholar 

  39. Manczinger M, Bocsik A, Kocsis GF et al (2015) The absence of N-acetyl-d-glucosamine causes attenuation of virulence of Candida albicans upon interaction with vaginal epithelial cells in vitro. Biomed Res Int. https://doi.org/10.1155/2015/398045

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mao D, Okada BK, Wu Y et al (2018) Recent advances in activating silent biosynthetic gene clusters in bacteria. Curr Opin Microbiol 45:156–163. https://doi.org/10.1016/j.mib.2018.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Matilla MA, Daddaoua A, Chini A et al (2018) An auxin controls bacterial antibiotics production. Nucleic Acids Res 46:11229–11238. https://doi.org/10.1093/nar/gky766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mo S, Kim J, Oh C-H (2013) Different effects of acidic pH shock on the prodiginine production in Streptomyces coelicolor M511 and SJM1 mutants. J Microbiol Biotechnol 23:1454–1459. https://doi.org/10.4014/jmb.1307.07067

    Article  CAS  PubMed  Google Scholar 

  43. Montaser R, Luesch H (2011) Marine natural products: a new wave of drugs? Future Med Chem 3:1475–1489. https://doi.org/10.4155/fmc.11.118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Moore JM, Bradshaw E, Seipke RF et al (2012) Chapter eighteen—use and discovery of chemical elicitors that stimulate biosynthetic gene clusters in Streptomyces bacteria. In: Hopwood DA (ed) methods in enzymology. Academic Press, Cambridge, pp 367–385

    Google Scholar 

  45. Motoyama T, Osada H (2016) Biosynthetic approaches to creating bioactive fungal metabolites: pathway engineering and activation of secondary metabolism. Bioorg Med Chem Lett 26:5843–5850. https://doi.org/10.1016/j.bmcl.2016.11.013

    Article  CAS  PubMed  Google Scholar 

  46. Moussian B (2008) The role of GlcNAc in formation and function of extracellular matrices. Comp Biochem Physiol B Biochem Mol Biol 149:215–226. https://doi.org/10.1016/j.cbpb.2007.10.009

    Article  CAS  PubMed  Google Scholar 

  47. Munshi A, Shafi G, Aliya N, Jyothy A (2009) Histone modifications dictate specific biological readouts. J Genet Genom 36:75–88. https://doi.org/10.1016/S1673-8527(08)60094-6

    Article  CAS  Google Scholar 

  48. Nah H-J, Pyeon H-R, Kang S-H et al (2017) Cloning and heterologous expression of a large-sized natural product biosynthetic gene cluster in Streptomyces species. Front Microbiol 8:1–10. https://doi.org/10.3389/fmicb.2017.00394

    Article  Google Scholar 

  49. Naseem S, Parrino SM, Buenten DM, Konopka JB (2012) Novel roles for GlcNAc in cell signaling. Commun Integr Biol 5:156–159. https://doi.org/10.4161/cib.19034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ochi K, Hosaka T (2013) New strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters. Appl Microbiol Biotechnol 97:87–98. https://doi.org/10.1007/s00253-012-4551-9

    Article  CAS  PubMed  Google Scholar 

  51. Okada BK, Seyedsayamdost MR (2017) Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules. FEMS Microbiol Rev 41:19–33. https://doi.org/10.1093/femsre/fuw035

    Article  CAS  PubMed  Google Scholar 

  52. Özkaya FC, Peker Z, Camas M et al (2017) Marine fungi against aquaculture pathogens and induction of the activity via co-culture: biotechnology. CLEAN Soil Air Water 45:1700238. https://doi.org/10.1002/clen.201700238

    Article  CAS  Google Scholar 

  53. Pacwa-Płociniczak M, Płaza GA, Piotrowska-Seget Z, Cameotra SS (2011) Environmental applications of biosurfactants: recent advances. Int J Mol Sci 12:633–654. https://doi.org/10.3390/ijms12010633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pál C, Hurst LD (2004) Evidence against the selfish operon theory. Trends Genet 20:232–234. https://doi.org/10.1016/j.tig.2004.04.001

    Article  CAS  PubMed  Google Scholar 

  55. Park HB, Kwon HC, Lee C-H, Yang HO (2009) Glionitrin A, an antibiotic–antitumor metabolite derived from competitive interaction between abandoned mine microbes. J Nat Prod 72:248–252. https://doi.org/10.1021/np800606e

    Article  CAS  PubMed  Google Scholar 

  56. Pimentel-Elardo SM, Sørensen D, Ho L et al (2015) Activity-independent discovery of secondary metabolites using chemical elicitation and cheminformatic inference. ACS Chem Biol 10:2616–2623. https://doi.org/10.1021/acschembio.5b00612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rateb ME, Hallyburton I, Houssen WE et al (2013) Induction of diverse secondary metabolites in Aspergillus fumigatus by microbial co-culture. RSC Adv 3:14444–14450. https://doi.org/10.1039/c3ra42378f

    Article  CAS  Google Scholar 

  58. Ren H, Wang B, Zhao H (2017) Breaking the silence: new strategies for discovering novel natural products. Curr Opin Biotechnol 48:21–27. https://doi.org/10.1016/j.copbio.2017.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rigali S, Anderssen S, Naômé A, van Wezel GP (2018) Cracking the regulatory code of biosynthetic gene clusters as a strategy for natural product discovery. Biochem Pharmacol 153:24–34. https://doi.org/10.1016/j.bcp.2018.01.007

    Article  CAS  PubMed  Google Scholar 

  60. Romano S, Jackson S, Patry S, Dobson A (2018) Extending the “One Strain Many Compounds” (OSMAC) principle to marine microorganisms. Mar Drugs 16:244. https://doi.org/10.3390/md16070244

    Article  CAS  PubMed Central  Google Scholar 

  61. Ross AC, Gulland LES, Dorrestein PC, Moore BS (2015) Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform. ACS Synth Biol 4:414–420. https://doi.org/10.1021/sb500280q

    Article  CAS  PubMed  Google Scholar 

  62. Rutledge PJ, Challis GL (2015) Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol 13:509–523. https://doi.org/10.1038/nrmicro3496

    Article  CAS  PubMed  Google Scholar 

  63. Seyedsayamdost MR (2014) High-throughput platform for the discovery of elicitors of silent bacterial gene clusters. Proc Natl Acad Sci USA 111:7266–7271. https://doi.org/10.1073/pnas.1400019111

    Article  CAS  PubMed  Google Scholar 

  64. Sharma R, Jamwal V, Singh VP et al (2017) Revelation and cloning of valinomycin synthetase genes in Streptomyces lavendulae ACR-DA1 and their expression analysis under different fermentation and elicitation conditions. J Biotechnol 253:40–47. https://doi.org/10.1016/j.jbiotec.2017.05.008

    Article  CAS  PubMed  Google Scholar 

  65. Shi Y, Pan C, Auckloo BN et al (2017) Stress-driven discovery of a cryptic antibiotic produced by Streptomyces sp. WU20 from Kueishantao hydrothermal vent with an integrated metabolomics strategy. Appl Microbiol Biotechnol 101:1395–1408. https://doi.org/10.1007/s00253-016-7823-y

    Article  CAS  PubMed  Google Scholar 

  66. Shu C-H, Tseng K, Jaiswal R (2018) Effects of light intensity and wavelength on the production of lactobionic acid from whey by Pseudomonas taetrolens in batch cultures: effects of light intensity and wavelength on the production of lactobionic acid. J Chem Technol Biotechnol 93:1595–1600. https://doi.org/10.1002/jctb.5528

    Article  CAS  Google Scholar 

  67. Skellam E (2018) Strategies for engineering natural product biosynthesis in fungi. Trends in Biotechnol. https://doi.org/10.1016/j.tibtech.2018.09.003

    Article  Google Scholar 

  68. Slawson C, Housley MP, Hart GW (2006) O-GlcNAc cycling: how a single sugar post-translational modification is changing the way we think about signaling networks. J Cell Biochem 97:71–83. https://doi.org/10.1002/jcb.20676

    Article  CAS  PubMed  Google Scholar 

  69. Smetanina OF, Yurchenko AN, Afiyatullov SS et al (2012) Oxirapentyns B–D produced by a marine sediment-derived fungus Isaria felina (DC.) Fr. Phytochem Lett 5:165–169. https://doi.org/10.1016/j.phytol.2011.12.002

    Article  CAS  Google Scholar 

  70. Stierle AA, Stierle DB, Decato D et al (2017) The berkeleylactones, antibiotic macrolides from fungal coculture. J Nat Prod 80:1150–1160. https://doi.org/10.1021/acs.jnatprod.7b00133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sung A, Gromek S, Balunas M (2017) Upregulation and identification of antibiotic activity of a marine-derived Streptomyces sp. via co-cultures with human pathogens. Mar Drugs 15:250. https://doi.org/10.3390/md15080250

    Article  CAS  PubMed Central  Google Scholar 

  72. Tanaka Y, Hosaka T, Ochi K (2010) Rare earth elements activate the secondary metabolite–biosynthetic gene clusters in Streptomyces coelicolor A3(2). J Antibiot 63:477–481. https://doi.org/10.1038/ja.2010.53

    Article  CAS  PubMed  Google Scholar 

  73. Timmermans M, Paudel Y, Ross A (2017) Investigating the biosynthesis of natural products from marine Proteobacteria: a survey of molecules and strategies. Mar Drugs 15:235. https://doi.org/10.3390/md15080235

    Article  CAS  PubMed Central  Google Scholar 

  74. Timmermans ML, Picott KJ, Ucciferri L, Ross AC (2018) Culturing marine bacteria from the genus Pseudoalteromonas on a cotton scaffold alters secondary metabolite production. Microbiol Open. https://doi.org/10.1002/mbo3.724

    Article  Google Scholar 

  75. Tong Y, Charusanti P, Zhang L et al (2015) CRISPR-Cas9 based engineering of actinomycetal genomes. ACS Synth Biol 4:1020–1029. https://doi.org/10.1021/acssynbio.5b00038

    Article  CAS  PubMed  Google Scholar 

  76. van der Meij A, Willemse J, Schneijderberg MA et al (2018) Inter- and intracellular colonization of Arabidopsis roots by endophytic actinobacteria and the impact of plant hormones on their antimicrobial activity. Antonie Van Leeuwenhoek 111:679–690. https://doi.org/10.1007/s10482-018-1014-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wang C, Huang D, Liang S (2018) Identification and metabolomic analysis of chemical elicitors for tacrolimus accumulation in Streptomyces tsukubaensis. Appl Microbiol Biotechnol 102:7541–7553. https://doi.org/10.1007/s00253-018-9177-0

    Article  CAS  PubMed  Google Scholar 

  78. Watrous JD, Dorrestein PC (2011) Imaging mass spectrometry in microbiology. Nat Rev Microbiol 9:683–694. https://doi.org/10.1038/nrmicro2634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wright GD (2017) Opportunities for natural products in 21st century antibiotic discovery. Nat Prod Rep 34:694–701. https://doi.org/10.1039/C7NP00019G

    Article  CAS  PubMed  Google Scholar 

  80. Xu D, Han L, Li C et al (2018) Bioprospecting deep-sea Actinobacteria for novel anti-infective natural products. Front Microbiol. https://doi.org/10.3389/fmicb.2018.00787

    Article  PubMed  PubMed Central  Google Scholar 

  81. Xu D, Nepal KK, Chen J et al (2018) Nocardiopsistins A–C: new angucyclines with anti-MRSA activity isolated from a marine sponge-derived Nocardiopsis sp. HB-J378. Synth Syst Biotechnol 3:246–251. https://doi.org/10.1016/j.synbio.2018.10.008

    Article  PubMed  PubMed Central  Google Scholar 

  82. Xu F, Nazari B, Moon K et al (2017) Discovery of a cryptic antifungal compound from Streptomyces albus J1074 using high-throughput elicitor screens. J Am Chem Soc 139:9203–9212. https://doi.org/10.1021/jacs.7b02716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Xu F, Wu Y, Zhang C et al (2019) A genetics-free method for high-throughput discovery of cryptic microbial metabolites. Nat Chem Biol 15:161. https://doi.org/10.1038/s41589-018-0193-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zeng Z, Cai X, Wang P et al (2017) Biofilm formation and heat stress induce pyomelanin production in deep-sea Pseudoalteromonas sp. SM9913. Front Microbiol 8:1822. https://doi.org/10.3389/fmicb.2017.01822

    Article  PubMed  PubMed Central  Google Scholar 

  85. Zhang MM, Wong FT, Wang Y et al (2017) CRISPR–Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol 13:607–609. https://doi.org/10.1038/nchembio.2341

    Article  CAS  Google Scholar 

  86. Zhang Z, He X, Zhang G et al (2017) Inducing secondary metabolite production by combined culture of Talaromyces aculeatus and Penicillium variabile. J Nat Prod 80:3167–3171. https://doi.org/10.1021/acs.jnatprod.7b00417

    Article  CAS  PubMed  Google Scholar 

  87. Zhu H, Sandiford SK, van Wezel GP (2014) Triggers and cues that activate antibiotic production by actinomycetes. J Ind Microbiol Biotechnol 41:371–386. https://doi.org/10.1007/s10295-013-1309-z

    Article  CAS  PubMed  Google Scholar 

  88. Zhuravleva OI, Afiyatullov SS, Vishchuk OS et al (2012) Decumbenone C, a new cytotoxic decaline derivative from the marine fungus Aspergillus sulphureus KMM 4640. Arch Pharmacal Res 35:1757–1762. https://doi.org/10.1007/s12272-012-1007-9

    Article  CAS  Google Scholar 

  89. Zou A, Liu J, Garamus VM et al (2010) Interaction between the natural lipopeptide [Glu1, Asp5] surfactin-C15 and hemoglobin in aqueous solution. Biomacromolecules 11:593–599. https://doi.org/10.1021/bm9011453

    Article  CAS  PubMed  Google Scholar 

  90. Zuck KM, Shipley S, Newman DJ (2011) Induced production of N-formyl alkaloids from Aspergillus fumigatus by co-culture with Streptomyces peucetius. J Nat Prod 74:1653–1657. https://doi.org/10.1021/np200255f

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Funding is gratefully acknowledged from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-06078) (Discovery Grant to ACR) and Queen’s University (Research Initiation Grant to ACR and Graduate award to LU).

Author information

Authors and Affiliations

  1. Department of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada

    Hailey A. Tomm, Lorena Ucciferri & Avena C. Ross

Authors
  1. Hailey A. Tomm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lorena Ucciferri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Avena C. Ross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Avena C. Ross.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tomm, H.A., Ucciferri, L. & Ross, A.C. Advances in microbial culturing conditions to activate silent biosynthetic gene clusters for novel metabolite production. J Ind Microbiol Biotechnol 46, 1381–1400 (2019). https://doi.org/10.1007/s10295-019-02198-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-019-02198-y

Keywords

Search

Navigation