A review on different approaches to isolate antibiotic compounds from fungi


  • Jyotsna Baby St. Thomas College Palai, Mahatma Gandhi University Kottayam
  • Toji Thomas St. Thomas College Palai, Mahatma Gandhi University Kottayam




co-culture, novel antibiotics, omics-based, secondary metabolites, mutasythesis


Fungal secondary metabolites are promising grounds of many antibiotic compounds; this happens because of the unique biosynthetic capabilities of the organism in adaptation with various environments. Some of the potential environmental conditions or habitats stimulate fungi to produce bioactive compounds; these include various stress factors like temperature, osmotic changes and pollution. Traditional approaches used to isolate fungal antibiotics are mainly mono-culture-based and it trails behind the ever-expanding needs of the clinical world. A recent progress made in the culture-based approach is the co-culture of microbes, which creates a competing environment for the fungi resulting in the induction of hidden biosynthetic pathways. The revolutionizing impacts of the post-genomic era also aided these search in the form of various omics-based and biosynthetic approaches. These approaches not only facilitate the invention of all-new compounds but contribute in the modification of existing compounds through which the compounds can serve as better drug candidates.


Albright JC, Henke T, Soukup AA, McClure RA, Regan J (2015) Large-scale metabolomics reveals of Aspergillus nidulans to epigenetic perturbation. ACS Chemical Biology 10(6):1535-1541. https://doi.org/10.1021/acschembio.5b00025

Awaad AS, Nabilah AJA, Zain ME (2012) New antifungal compounds from Aspergillus terreus isolated from desert soil. Phytotherapy Research 26(12):1872–1877. https://doi.org/10.1002/ptr.4668

Bai H, Xue X, Hou Z, Zhou Y, Meng J, Luo X (2010) Antisense antibiotics: a brief review of novel target discovery and delivery. Current drug discovery technologies 7(2):76–85. https://doi.org/10.2174/157016310793180594

Bailey AM, Alberti F, Kilaru S, Collins CM, de Mattos-Shipley K, Hartley AJ, Hayes P, Griffin A, Lazarus CM, Cox RJ, Willis CL, Dwyer KO, Spence DW, Foster GD (2016) Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production. Scientific Reports 6(1):25202. https://doi.org/10.1038/srep25202

Berdy J (2012) Thoughts and facts about antibiotics: where are we now and where are we heading. The Journal of antibiotics 65(8):385–395. https://doi.org/10.1038/ja.2012.27

Bergmann S, Schumann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKSNRPS hybrid metabolites from Aspergillus nidulans. Nature Chemical Biology 3(4):213–217. https://doi.org/10.1038/nchembio869

Bharadwaj A, Chaman S, Verma S (2017) Production of antibacterial agent from fungi isolated from pharmaceutical soil sample by fermentation under optimized conditions. Asian Journal of Pharmaceutical and Clinical research 10(7):110-115. https://doi.org/10.22159/ajpcr.2017.v10i7.18258

Blondelle SE, Houghten RA (1992) Design of model amphipathic peptides having potent antimicrobial activities. Biochemistry 31(50):12688–12694. https://doi.org/10.1021/bi00165a020

Blondelle SE, Lohner K (2000) Combinatorial Libraries: A tool to design antimicrobial and antifungal peptide analogues having lytic specificities for structure – activity relationship studies. Peptide Science 55(1):74–87. https://doi.org/10.1002/1097-0282(2000)55:1%3C74::AID-BIP70%3E3.0.CO;2-S

Blondelle SE, Ostresh JM, Houghten RA, Perez-Paya E (1995) Induced conformational states of amphipathic peptides in aqueous /lipid environments. Biophysical Journal 68(1):351–359. https://doi.org/10.1016/S0006-3495(95)80194-3

Blondelle SE, Takahashi E, Houghten RA, Perez-Paya E (1996) Rapid identification of compounds with enhanced antimicrobial activity by using conformationally defined combinatorial libraries. Biochemical Journal 313(1):141–147. https://doi.org/10.1042/bj3130141

Boecker S, Zobel S, Meyer V, Sussmuth RD (2016) Rational biosynthetic approaches for the production of new-to-nature compounds in fungi. Fungal Genetics and Biology 89(4):89-101. https://doi.org/10.1016/j.fgb.2016.02.003

Bok JW, Hoffmeister D, Maggio-Hall LA, Murillo R, Glasner JD, Keller NP, Rica C (2006) Genomic Mining for Aspergillus natural products. Chemistry & Biology 13(1):31–37. https://doi.org/10.1016/j.chembiol.2005.10.008

Brandl E, Margreiter H (1954). Ein saurestabiles biosynthetisches Penicillin. Öesterreiche Chemikee Zeitung 55:11.

Cain JW, Miller KI, Kelaitzis JA, Chau R, Neilan BA (2020) Genome mining of a fungal endophyte of Taxus yunnanensis (Chinese yew) leads to the discovery of a novel azaphilone polyketide, lijiquinone. Microbial Biotechnology 13(5):1415-1427. https://doi.org/10.1111/1751-7915.13568

Challis GL (2008) Mining microbial genomes for new natural products and biosynthetic pathways. Microbiology 154(6):1555–1569. https://doi.org/10.1099/mic.0.2008/018523-0

Chandra N, Kumar S (2017) Antibiotics and antibiotics resistance genes in soils. Soil Biology 51(11):1–18. https://doi.org/10.1007/978-3-319-66260-2

Chiang Y, Szewczyk E, Nayak T, Davidson AD, Sanchez JF, Lo H, Ho W, Simityan H, Kuo E, Praseuth A, Watanabe K, Oakley BR, Wang CCC (2008) Molecular genetic mining of the Aspergillus secondary metabolome: discovery of the emericellamide biosynthetic pathway. Chemistry & Biology 15(6):527–532. https://doi.org/10.1016/j.chembiol.2008.05.010

Cimermancic P, Medema MH, Claesen J, Kurita K, Wieland Brown LC, Mavrommatis K, Pati A, Godfrey PA, Koehrsen M, Clardy J, Birren BW, Takano E, Sali A, Linington RG, Fischbach MA (2014) Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 158(2):412–421. https://doi.org/10.1016/j.cell.2014.06.034

Corley DG, Durley RC (1994) Strategies for database dereplication of natural products. Journal of Natural Products 57(11):1484–1490. https://doi.org/10.1021/np50113a002

Cueto M, Jensen PR, Kauffman CA, Fenical W, Lobkovsky E, Clardy J (2001) Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge. Journal of Natural Products 64(11):1444-1446. https://doi.org/10.1021/np0102713

Davies J (1985) Recombinant DNA and the production of small molecules. ASM Press, Washington DC, 364 366

Degenkolb T, Heinze S, Schlegel B, Strobel G, Gräfe U (2002) Formation of new lipoaminopeptides, acremostatins A, B, and C, by co-cultivation of Acremonium sp. Tbp-5 and Mycogone rosea DSM 12973. Bioscience Biotechnology and Biochemistry 66(4):883–886. https://doi.org/10.1271/bbb.66.883

Fleming A (1929) On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae. The British Journal of Experimental Pathology 10(2):226-236.

Floss HG (2006) Combinatorial biosynthesis- Potential and problems. Journal of Biotechnology 124(1):242–257. https://doi.org/10.1016/j.jbiotec.2005.12.001

Frisvad JC, Smedsgaard J, Larsen TO, Samson RA (2004) Mycotoxins, drugs and other extrolites produced by species in Penicillium subgenus Penicillium. Studies in Mycology 49:201–241.

Gaudencio SP, Pereira F (2015) Dereplication: racing to speed up the natural products discovery process. Natural Product Reports 32(6):779–810. https://doi.org/10.1039/C4NP00134F

Godinho VM, Gonçalves VN, Santiago IF, Figueredo HM, Vitoreli GA, Schaefer CEGR, Barbosa EC, Oliveira GJ, Alves TMA, Zani CL, Junior ASP, Murta SMF, Romanha AJ, Kroon EG, Cantrell CL, Wedge DE, Duke OS, Ali A, Rosa AC, Rosa HL (2015) Diversity and bioprospection of fungal community present in oligotrophic soil of continental Antarctica. Extremophiles 19(3):585–596. https://doi.org/10.1007/s00792-015-0741-6

Gomez-Flores M, Nakhla G, Hafez H (2017) Hydrogen production and microbial kinetics of Clostridium termitidis in mono-culture and co-culture with Clostridium beijerinckii. AMB Express 7(1):84-96. https://doi.org/10.1186/s13568-016-0256-2

Gross H (2007) Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. Applied Microbiology and Biotechnology 75(2):267–277. https://doi.org/10.1007/s00253-007-0900-5

Gross H (2009) Genomic mining-a concept for the discovery of new bioactive natural products. Current Opinion in Drug Discovery and Development 12(2):207−219.

Gross H, Stockwell VO, Henkels MD, Nowak-Thompson B, Loper JE, Gerwick WH (2007) The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters. Chemistry and Biology 14(1):53–63. https://doi.org/10.1016/j.chembiol.2006.11.007

Hauser TJ (2006) Techniques for studying bacteria and fungi. Carolina Biological Supply Company, North Carolina, pp 3-10.

Hautbergue T, Jamin EL, Debrauwer L, Puel O (2018) From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites. Natural Product Reports 35(2):147–173. https://doi.org/10.1039/C7NP00032D

He F, Li X, Yu J, Zhang X, Nong X, Chen G (2019) Secondary metabolites from the mangrove sediment-derived fungus Penicillium pinophilum SCAU037. Fitoterapia 136(4):104177. https://doi.org/10.1016/j.fitote.2019.104177

Hopwood DA, Malpartida F, Kieser HM, Ikeda H, Duncan J, Fujii I, Rudd BAM, Floss HG, Omura S (1985) Production of ‘hybrid’ antibiotics by genetic engineering. Nature 314(4):642–644. https://doi.org/10.1038/314642a0

Horai H, Arita M, Kanaya S, Nihei Y, Ikeda T, Suwa K, Ojima Y, Tanaka K, Tanaka Y, Aoshima K, Oda Y, Kakazu K, Kusano M, Tohge T, Matsuda F, Sawada Y, Hirai MY, Nakanishi H, Ikeda K, Akimoto N, Maoka T, Takahashi H, Ara T, Sakurai N, Suzuki H, Shibata D, Neumann S, Iida T, Tanaka, K, Funatsu K, Matsuura F, Soga T, Taguchi R, Saito K, Nishioka T (2010) MassBank: a public repository for sharing mass spectral data for life sciences. Journal of Mass Spectrometry 45(7):703–714. https://doi.org/10.1002/jms.1777

Houghten RA, Pinilla C, Blondelle SE, Appel JR, Dooley CT, Cuervo JH (1991) Generation and use of synthetic peptide combinatorial libraries for basic research and discovery. Nature 354(6348):84–86. https://doi.org/10.1038/354084a0

Idle JR, Gonzalez FJ (2007) Metabolomics. Cell Metabolism 6(5):348–351. https://doi.org/10.1016/j.cmet.2007.10.005

Johnson DB, Hallberg KB (2003) The microbiology of acidic mine waters. Research in Microbiology 154(7):466–473. https://doi.org/10.1016/S0923-2508(03)00114-1

Kathiresan K, Bingham BL (2001) Biology of mangroves and mangrove ecosystem. Advances in marine biology 40:81-82. https://doi.org/10.1016/S0065-2881(01)40003-4

Kealey C, Creaven, CA, Murphy CD, Brady CB (2017) New approaches to antibiotic discovery. Biotechnology Letters 39(6):805-817. https://doi.org/10.1007/s10529-017-2311-8

Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism—from biochemistry to genomics. Nature Reviews Microbiology 3(12):937-947. https://doi.org/10.1038/nrmicro1286

Kind T, Fiehn O (2010) Advances in structure elucidation of small molecules using mass spectrometry. Bioanalytical Reviews 2(12):23–60. https://doi.org/10.1007/s12566-010-0015-9

Kirschning A, Hahn F (2012) Merging chemical synthesis and biosynthesis: a new chapter in the total synthesis of natural products and natural product libraries. Angewandte Chemie International Edition 51(17):4012–4022. https://doi.org/10.1002/anie.201107386

Klitgaard A, Nielsen JB, Frandsen RJN, Andersen MR, Nielsen KF (2015) Combining stable isotope labeling and molecular networking for biosynthetic pathway characterization. Analytical Chemistry 87(13):6520–6526. https://doi.org/10.1021/acs.analchem.5b01934

Konig CC, Scherlach K, Schroeckh V, Horn F, Nietzsche S, Brakhage AA, Hertweck C (2013) Bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus Aspergillus fumigatus. ChemBioChem 14(8):938-942. https://doi.org/10.1002/cbic.201300070

Kristiansson E, Fick J, Janzon A, Garbi R, Rutgersson C, Weijdegard B (2011) Pyrosequencing of antibiotic contaminated river sediment reveals high levels of resistance and gene transfer elements. PLOS ONE 6(2):e17038. https://doi.org/10.1371/journal.pone.0017038

Kuck U, Bloemendal S, Teichert I (2014) Putting fungi to work: harvesting a cornucopia of drugs, toxins and antibiotics. PLOS Pathogens 10(3):e1003950. https://doi.org/10.1371/journal.ppat.1003950

Laatsch H (2014) Antibase 2014: The natural compound identifier. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. https://www.mswil.com/software/spectral-libraries-and-databases/wiley-spectral-libraries/wiley-lc-ms-libraries/antibase-2014/

Li Y, Sun B, Liu S, Jiang L, Liu X, Zhang H, Che Y (2008) Bioactive asterric acid derivatives from the Antarctic ascomycete fungus Geomyces sp. Journal of Natural Products 71(9):1643–1646. https://doi.org/10.1021/np8003003

Liu R, Asad R, Khan A, Yue Q, Jiao Y, Yang Y, Li Y, Xie B (2020) Discovery of a new antifungal lipopeptaibol from Purpureocillium lilacinum using MALDI-TOF-IMS. Biochemical and Biophysical Research Communications 527(3):689-695. https://doi.org/10.1016/j.bbrc.2020.05.021

Liu Z, Dong Z, Qiu P, Wang Q, Yan J, Lu Y, Wasu PA, Hong K, She Z (2018) Two new bioactive steroids from a mangrove-derived fungus Aspergillus sp. Steroids 140(12):32-38. https://doi.org/10.1016/j.steroids.2018.08.009

Lo Giudice A, Fani R (2016) Antimicrobial potential of cold-adapted bacteria and fungi from Polar Regions. In: Biotechnology of extremophiles (Rampeletto P, ed), Grand Challenges in Biology and Biotechnology, vol 1. Springer, Cham, pp 83-115. https://doi.org/10.1007/978-3-319-13521-2_3

Machado H, Tuttle RN, Jensen PR (2017) Omics-based natural product discovery and the lexicon of genome mining. Current Opinion in Microbiology 39(10):136–142. https://doi.org/10.1016/j.mib.2017.10.025

Madigan MT, Martinko JM, Parker J, Brock TD (1997). Brock biology of microorganisms. Upper Saddle River, NJ, Prentice Hall.

Meng L, Liu Y, Li X, Xu G, Ji N, Wang B (2015) Citrifelins A and B, citrinin adducts with a tetracyclic framework from co-cultures of marine-derived isolates of Penicillium citrinum and Beauveria felina. Journal of Natural Products 78(9):2301–2305. https://doi.org/10.1021/acs.jnatprod.5b00450

Mohimani H, Gurevich A, Mikheenko A, Garg N, Nothias LF, Ninomiya A, Takada K, Dorrestein PC, Pevzner PA (2017) Dereplication of peptidic natural products through database search of mass spectra. Nature Chemical Biology 13(1):30–37. https://doi.org/10.1038/nchembio.2219

Mohimani H, Liu WT, Kersten RD, Moore BS, Dorrestein PC, Pevzner PA (2014) NRPquest: coupling mass spectrometry and genome mining for non ribosomal peptide discovery. Journal of Natural Products 77(8):1902–1909. https://doi.org/10.1021/np500370c

Mohimani H, Pevzner PA (2016) Dereplication, sequencing and identification of peptidic natural products: from genome mining to peptidogenomics to spectral networks. Natural Product Reports 33(10):73–86. https://doi.org/10.1039/C5NP00050E

Molloy EM, Hertweck C (2017) Antimicrobial discovery inspired by ecological interactions. Current Opinion in Microbiology 39(10):121-127. https://doi.org/10.1016/j.mib.2017.09.006

Montiel PO (2000) Soluble carbohydrates (trehalose in particular) and cryoprotection in polar biota. Cryo Letters 21(2):83–90.

Netzker T, Fischer J, Weber J, Mattern DJ, König CC, Valiante V, Schroeckh V, Brakhage AA (2015) Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Frontiers in Microbiology 6(3):1–13. https://doi.org/10.3389/fmicb.2015.00299

Netzker T, Flak M, Krespach MKC, Stroe MC, Weber J, Schroeckh V, Brakhage AA (2018) Microbial interactions trigger the production of antibiotics. Current Opinion in Microbiology 45(10):117–123. https://doi.org/10.1016/j.mib.2018.04.002

Neumann S, Bocker S (2010) Computational mass Spectrometry for metabolomics: identification of metabolites and small molecules. Analytical and Bioanalytical Chemistry 398(10):2779–2788. https://doi.org/10.1007/s00216-010-4142-5

Nikolouli K, Mossialos D (2012) Bioactive compounds synthesized by non-ribosomal peptide synthetases and type-I polyketide synthases discovered through genome-mining and metagenomics. Biotechnology Letters 34(10):1393-1403. https://doi.org/10.1007/s10529-012-0919-2

Nilanonta C, Isaka M, Kittakoop P, Trakulnaleamsai S, Tanticharoen M, Thebtaranonth Y (2002) Precursor-directed biosynthesis of beauvericin analogues by the insect pathogenic fungus Paecilomyces tenuipes BC 1614. Tetrahedron 58(17):3355–3360. https://doi.org/10.1016/S0040-4020(02)00294-6

Nishiyama T (1977) Studies on evaporite minerals from Dry Valley, Victoria Land, Antarctica. Antarctic Research 58:171–185.

Nonaka K, Abe T, Iwatsuki M, Mori M, Yamamoto T, Shiomi K, Omura S, Masuma R (2011) Enhancement of metabolites productivity of Penicillium pinophilum FKI-5653, by co-culture with Trichoderma harzianum FKI-5655. The Journal of Antibiotics 64(12):769–774. https://doi.org/10.1038/ja.2011.91

Oh DC, Kauffman CA, Jensen PR, Fenical W (2007) Induced production of emericellamide A and B from the marine-derived fungus Emericella sp. in competing co-culture. Journal of Natural Products 70(4):515-520. https://doi.org/10.1021/np060381f

Olano C, Mendez C, Salas JA (2014) Strategies for the design and discovery of novel antibiotics using genetic engineering and genome mining. In: Antimicrobial compounds (Villa T, Viega-Crespo P, eds). Springer, Berlin Heidelberg, pp 1-25. https://doi.org/10.1007/978-3-642-40444-3_1

Ondeyka JG, Zink DL, Young K, Painter R, Kodali S, Galgoci A, Collado J, Tormo JR, Basilio A, Vicente F, Wang J, Singh SB (2006) Discovery of bacterial fatty acid synthase inhibitors from a Phoma Species as antimicrobial agents using a new antisense-based strategy. Journal of Natural Products 69(3):377-380. https://doi.org/10.1021/np050416w

Oppong-Danquah E, Passaretti C, Chianese O, Blümel M, Tasdemir D (2020) Mining the metabolome and the agricultural and pharmaceutical potential of sea foam-derived fungi. Marine Drugs 18(2):128. https://doi.org/10.3390/md18020128

Palazzotto E, Weber T (2018) Omics and multi-omics approaches to study the biosynthesis of secondary metabolites in microorganisms. Current Opinion in Microbiology 45(10):109–116. https://doi.org/10.1016/j.mib.2018.03.004

Parish CA, Cruz M, De Smith SK, Zink D, Baxter J, Tucker-Samaras S, Collado J, Platas G, Bills G, Dıez MT, Vicente F, Pelaez F, Wilson K (2009) Antisense-guided isolation and structure elucidation of pannomycin, a substituted cis-decalin from Geomyces pannorum. Journal of Natural Products 72(1):59–62. https://doi.org/10.1021/np800528a

Park HB, Kwon HC, Lee CH, Yang HO (2009) Glionitrin A, an antibiotic - antitumor metabolite derived from competitive interaction between abandoned mine microbes. Journal of Natural Products 72(2):248–252. https://doi.org/10.1021/np800606e

Patti GJ (2011) Separation strategies for untargeted metabolomics. Journal of separation science 34(24):3460-3469. https://doi.org/10.1002/jssc.201100532

Perez-Paya E, Houghten RA, Blondelle S E (1996) Functionalized protein-like structures from conformationally defined synthetic combinatorial libraries. Journal of Biology and Chemistry 271(8):4120–4126. https://doi.org/10.1074/jbc.271.8.4120

Pinilla C, Appel JR, Blanc P, Houghten RA (1992) Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 13(6):901– 905.

Roberts LD, Souza AL, Gerszten RE, Clish CB (2012) Targeted Metabolomics. Current Protocols in Molecular Biology 98(1):30.2.1-30.2.24. https://doi.org/10.1002/0471142727.mb3002s98

Sanglier JJ, Haag H, Huck TA, Fehr T (1996) Section review; anti-infectives: review of actinomycetes compounds: 1990-1995. Expert Opinion on Investigational Drugs 5(2):207-223. https://doi.org/10.1517/13543784.5.2.207

Santiago IF, Alves TMA, Rabello A, Sales-Junior PA, Romanha AJ, Zani CL, Rosa AC, Rosa LH (2012) Leishmanicidal and antitumoral activities of endophytic fungi associated with the Antarctic angiosperms Deschampsia antarctica Desv. and Colobanthus quitensis (Kunth) Bartl. Extremophiles 16(1):95–103. https://doi.org/10.1007/s00792-011-0409-9

Sawada Y, Nakabayashi R, Yamada Y, Suzuki M, Sato M, Sakata A, Akiyama K, Sakurai T, Matsuda F, Aoki T, Hirai MY, Saito K (2012) RIKEN tandem mass spectral database (ReSpect) for phytochemicals: a plant-specific MS/MS based data resource and database. Phytochemistry 82(10):38–45. https://doi.org/10.1016/j.phytochem.2012.07.007

Scheffler RJ, Colmer S, Tynan H, Demain AL, Gullo VP (2013) Antimicrobials, drug discovery, and genome mining. Applied microbiology and biotechnology 97(3):969–978. https://doi.org/10.1007/s00253-012-4609-8

Scherlach K, Hertweck C (2009) Triggering cryptic natural product biosynthesis in microorganisms. Organic and Biomolecular Chemistry 7(9):1753−1760. https://doi.org/10.1039/B821578B

Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, Mclean JA (2016) Untargeted metabolomics strategies — challenges and emerging directions. Journal of the American Society for Mass Spectrometry 27(12):1897-1905. https://doi.org/10.1007/s13361-016-1469-y

Schroeckh V, Scherlach K, Nutzmann HW, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009) Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proceedings of the National Academy of Sciences of the United States of America 106(34):14558-14563. https://doi.org/10.1073/pnas.0901870106

Shlaes DM (2010) Antibiotics: The perfect storm. Springer Science and Business Media, Dordrecht, pp 29-50. https://doi.org/10.1007/978-90-481-9057-7

Smedsgaard J, Nielsen J (2004) Metabolite profiling of fungi and yeast: from phenotype to metabolome by MS and informatics. Journal of Experimental Botany 56(410):273–286. https://doi.org/10.1093/jxb/eri068

Smith CA, Want EJ, O'Maille G, Abagyan R, Siuzdak G (2006) XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Analytical Chemistry 78(3):779–787. https://doi.org/10.1021/ac051437y

Stierle AA, Stierle DB, Decado D, Priestley ND, Alverson JB, Hoody J, Mcgrath K, Klepacki, D (2017) The berkeleylactones, antibiotic macrolide from fungal co-culture. Journal of Natural Products 80(4):1150-1160. https://doi.org/10.1021/acs.jnatprod.7b00133

Sussmuth R, Muller J, von Dohren H, Molnar I (2011) Fungal cyclooligomerdepsipeptides: from classical biochemistry to combinatorial biosynthesis. Natural Product Reports 28(1):99–124. https://doi.org/10.1039/c001463j

Svahn KS, Chryssanthou E, Olsen B, Bohlin L, Göransson U (2015) Penicillium nalgiovense Laxa isolated from Antarctica is a new source of the antifungal metabolite amphotericin B. Fungal Biology and Biotechnology 2(1). https://doi.org/10.1186/s40694-014-0011-x

Svahn KS, Goransson H, El-Seedi L, Bohlin DG, Larsson J, Olsen B, Chryssanthou E (2012) Antimicrobial activity of filamentous fungi isolated from highly antibiotic contaminated river sediment. Infection Ecology and Epidemology 2(1):11591. https://doi.org/10.3402/iee.v2i0.11591

Thatoi H, Behera BC, Mishra RR, Dutta SK (2013) Biodiversity and biotechnological potential of microorganisms from mangrove ecosystems: a review. Annals of Microbiology 63(3):1–19. https://doi.org/10.1007/s13213-012-0442-7

Tracanna V, de Jong A, Medema MH, Kuipers OP (2017) Mining prokaryotes for antimicrobial compounds: From diversity to function. FEMS Microbiology Reviews 41(3):417–429. https://doi.org/10.1093/femsre/fux014

Van den Berg MA, Albang R, Albermann K, Badger JH, Daran J, Driessen AJM, Garcia-Estrada C, Fedorova ND, Harris DM, Heijne WHM, Nierman WC, Joardar V, Kiel JAKW, Kovalchuk A, Martı JF, Nijland JG, Pronk JT, Roubos JA, van der Klei IJ, van Peij Noel NME, Veenhuis M, von Dohren H, Wagner C, Wortman J, Bovenerg Roel AL (2008) Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum. Nature Biotechnology 26(10):1161–1168. https://doi.org/10.1038/nbt.1498

Van der Hooft JJJ, Wandy J, Barrett MP, Burgess KEV, Rogers S (2016) Topic modelling for untargeted substructure exploration in metabolomics. Proceedings of the National Academy of Sciences of the United States of America 113(48):13738–13743. https://doi.org/10.1073/pnas.1608041113

Vieira G, Puric J, Morão LG, dos Santos JA, Inforsato FJ, Sette LD, Ferreira H, Sass DC (2018) Terrestrial and marine Antarctic fungi extracts active against Xanthomonas citri subsp. citri. Letters in Applied Microbiology 67(1):64–71. https://doi.org/10.1111/lam.12890

Walsh CT, Chen H, Keating TA, Hubbard BK, Losey HC, Luo L, Marshall CG, Miller DA, Patel HM (2001) Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines. Current Opinion in Chemical Biology 5(5):525–534. https://doi.org/10.1016/S1367-5931(00)00235-0

Wang G, Liu Z, Lin R, Li E, Mao Z, Ling J, Yang Y, Yin WB, Xie, B (2016) Biosynthesis of antibiotic leucinostatins in bio-control fungus Purpureocillium lilacinum and their inhibition on Phytophthora revealed by genome mining. PLOS Pathogen 12(7):1–30. https://doi.org/10.1371/journal.ppat.1005685

Weist S, Süssmuth RD (2005) Mutational biosynthesis- a tool for the generation of structural diversity in the biosynthesis of antibiotics. Applied Microbiology and Biotechnology 68(8):141–150. https://doi.org/10.1007/s00253-005-1891-8

Woodford N, Wareham DW (2009) Tackling antibiotic resistance: a dose of common antisense. Journal of Antimicrobial Chemotherapy 63(2):225-29. https://doi.org/10.1093/jac/dkn467

Wu C, Kim HK, Van Wezel GP, Choi YH (2015) Metabolomics in the natural products field - A gateway to novel antibiotics. Drug Discovery Today: Technologies 13(6):11–17. https://doi.org/10.1016/j.ddtec.2015.01.004

Xu J (2015) Bioactive natural products derived from mangrove-associated microbes. RSC Advances 5(2):841–892. https://doi.org/10.1039/C4RA11756E

Xu Y, Wijeratne EMK, Espinosa-Artiles P, Gunatilaka AAL, Molnar I (2009) Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer depsipeptide cell migration inhibitors from Beauveria bassiana. ChemBioChem 10(2):345–354. https://doi.org/10.1002/cbic.200800570

Yogabaanu U, Weber JFF, Convey P, Rizman-Idid M, Alias SA (2017) Antimicrobial properties and the influence of temperature on secondary metabolite production in cold environment soil fungi. Polar Science 14(12):60-67. https://doi.org/10.1016/j.polar.2017.09.005

Young K, Jayasuriya H, Ondeyka JG, Herath K, Zhang C, Kodali S, Galgoci A, Painter R., Brown-Driver V, Yamamoto R, Silver LL, Zheng Y, Ventura JI, Sigmund J, Ha S, Basilio A, Vicente F, Tormo JR, Pelaez F, Youngman P, Cully D, Barrett JF, Schmatz D, Singh SB, Wang J (2006) Discovery of FabH/FabF inhibitors from natural products. Antimicrobial Agents and Chemotherapy 50(2):519–526. https://doi.org/10.1128/aac.50.2.519-526.2006

Zerikly M, Challis GL (2009) Strategies for the discovery of new natural products by genome mining. ChemBioChem 10(4):625–633. https://doi.org/10.1002/cbic.200800389

Zhang C, Ondeyka JG, Zink DL, Basilio A, Vicente, F, Collado J, Platas G, Huber J, Dorso K, Motyl M, Byrne K, Singh SB (2009) Isolation, structure and antibacterial activity of pleosporone from a pleosporalean ascomycete discovered by using antisense strategy. Bioorganic & Medicinal Chemistry 17(6):2162–2166. https://doi.org/10.1016/j.bmc.2008.04.018

Ziemert N, Alanjary M, Weber T (2016) The evolution of genome mining in microbes – a review. Natural Product Reports 33(8):988–1005. https://doi.org/10.1039/C6NP00025H

Zobel S, Boecker S, Kulke D, Heimbach D, Meyer V, Süssmuth RD (2016) Reprogramming the biosynthesis of cyclodepsipeptide synthetases to obtain new enniatins and beauvericins. ChemBiochem 17(4):283-287. https://doi.org/10.1002/cbic.201500649




How to Cite

Baby, J., & Thomas, T. (2021). A review on different approaches to isolate antibiotic compounds from fungi. Italian Journal of Mycology, 50, 99–116. https://doi.org/10.6092/issn.2531-7342/12700