Secondary metabolites of a marine-derived Penicillium ochrochloron


  • Peter M. EZE Nnamdi Azikiwe University, Faculty of Health Sciences and Technology, Department of Environmental Health Sciences, Awka (NG)
  • Ying GAO Heinrich Heine University, Institute of Pharmaceutical Biology and Biotechnology, Düsseldorf (DE)
  • Yang LIU Justus Liebig University, Institute for Insect Biotechnology, Gießen (DE)
  • Lasse van GEELEN Heinrich Heine University, Institute of Pharmaceutical Biology and Biotechnology, Düsseldorf (DE)
  • Chika P. EJIKEUGWU Ebonyi State University, Department of Applied Microbiology, Abakiliki (NG)
  • Charles O. ESIMONE Nnamdi Azikiwe University, Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Microbiology and Biotechnology, Awka (NG)
  • Festus B. C. OKOYE Nnamdi Azikiwe University, Faculty of Pharmaceutical Sciences, Department of Pharmaceutical and Medicinal Chemistry, Awka (NG)
  • Peter PROKSCH Heinrich Heine University, Institute of Pharmaceutical Biology and Biotechnology, Düsseldorf (DE)
  • Rainer KALSCHEUER Heinrich Heine University, Institute of Pharmaceutical Biology and Biotechnology, Düsseldorf (DE)



drug discovery, marine fungus, natural products, Penicillium ochrochloron, secondary metabolites


Extremophilic fungi have received considerable attention recently as new promising sources of biologically active compounds with potential pharmaceutical applications. This study investigated the secondary metabolites of a marine-derived Penicillium ochrochloron isolated from underwater sea sand collected from the North Sea in St. Peter-Ording, Germany. Standard techniques were used for fungal isolation, taxonomic identification, fermentation, extraction, and isolation of fungal secondary metabolites. Chromatographic separation and spectroscopic analyses of the fungal secondary metabolites yielded eight compounds: talumarin A (1), aspergillumarin A (2), andrastin A (3), clavatol (4), 3-acetylphenol (5), methyl 2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furanpropanoate (6), emodin (7) and 2-chloroemodin (8). After co-cultivation with Bacillus subtilis, the fungus was induced to express (-)-striatisporolide A (9). Compound 1 was evaluated for antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Mycobacterium smegmatis, and M. tuberculosis, as well as cytotoxicity against THP-1 cells. The compound, however, was not cytotoxic to THP-1 cells and had no antibacterial activity against the microorganisms tested. The compounds isolated from P. ochrochloron in this study are well-known compounds with a wide range of beneficial biological properties that can be explored for pharmaceutical, agricultural, or industrial applications. This study highlights the bioprospecting potential of marine fungi and confirms co-cultivation as a useful strategy for the discovery of new natural products.


Metrics Loading ...


Abdel-Wahab NM, Scharf S, Özkaya FC, Kurtán T, Mándi A, Fouad MA, … Proksch P (2019). Induction of secondary metabolites from the marine-derived fungus Aspergillus versicolor through co-cultivation with Bacillus subtilis. Planta Medica 85(06):503-512.

Ancheeva E, Küppers L, Akone SH, Ebrahim W, Liu Z, Mándi A, … Proksch P (2017). Expanding the metabolic profile of the fungus Chaetomium sp. through co‐culture with autoclaved Pseudomonas aeruginosa. European Journal of Organic Chemistry 2017(22):3256-3264.

Butinar L, Frisvad JC, Gunde‐Cimerman N (2011). Hypersaline waters – a potential source of foodborne toxigenic aspergilli and penicillia. FEMS Microbiology Ecology 77(1):186-199.

Caro Y, Anamale L, Fouillaud M, Laurent P, Petit T, Dufosse L (2012). Natural hydroxyanthraquinoid pigments as potent food grade colorants: an overview. Natural Products and Bioprospecting 2(5):174-193.

Chang CH, Lin CC, Yang JJ, Namba T, Hattori M (1996). Anti-inflammatory effects of emodin from Ventilago leiocarpa. The American Journal of Chinese Medicine 24:139-142.

CLSI (2012). Methods for Dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Clinical and Laboratory Standards Institute (9th ed), USA.

Cohen PA, Hudson JB, Towers GHN (1996). Antiviral activities of anthraquinones, bianthrones and hypericin derivatives from lichens. Experientia 52:180-183.

da Silva BF, Rodrigues-Fo E (2010). Production of a benzylated flavonoid from 5,7,3′,4′,5′-pentamethoxyflavanone by Penicillium griseoroseum. Journal of Molecular Catalysis B: Enzymatic 67:184-188.

da Silva JV, Fill TP, da Silva BF, Rodrigues-Fo E (2013). Diclavatol and tetronic acids from Penicillium griseoroseum. Natural Product Research 27(1):9-16.

Daletos G, Kalscheuer R, Koliwer-Brandl H, Hartmann R, de Voogd NJ, Wray V, Lin W, Proksch P (2015). Callyaerins from the marine sponge Callyspongia aerizusa: cyclic peptides with antitubercular activity. Journal of Natural Products 78(8):1910-1925.

Deska J, Bäckvall J (2009). Enzymatic kinetic resolution of primary allenic alcohols. Application to the total synthesis and stereochemical assignment of striatisporolide A. Organic & Biomolecular Chemistry 7:3379-3381.

Eze PM, Abonyi DO, Abba CC, Proksch P, Okoye FBC, Esimone CO (2019). Toxic, but beneficial compounds from endophytic fungi of Carica papaya. The EuroBiotech Journal 3(2):105-111.

Frisvad JC, Rank C, Nielsen KF, Larsen TO (2009). Metabolomics of Aspergillus fumigatus. Medical Mycology 47(1):S53-71.

Frisvad JC (1989). The connection between the Penicillia and Aspergilli and mycotoxins with special emphasis on misidentified isolates. Archives of Environmental Contamination and Toxicology 18:452-467

Gomes DNF, Cavalcanti MAQ, Fernandes MJS, Lima DMM, Passavante JZO (2008). Filamentous fungi isolated from sand and water of “Bairro Novo” and “Casa Caiada” beaches, Olinda, Pernambuco, Brazil. Brazilian Journal of Biology 68(3):577-582.

Imhoff JF, Labes A, Wiese J (2011). Biomining the microbial treasures of the ocean: New natural products. Biotechnology Advances 29:468-482.

Imhoff JF (2016). Natural products from marine fungi--still an underrepresented resource. Marine Drugs 14(1):19.

Ismaiel AA, Rabie GH, Abd El-Aal MA (2016). Antimicrobial and morphogenic effects of emodin produced by Aspergillus awamori WAIR120. Biologia 71:464-474.

Jones EBG (2000). Marine fungi: some factors influencing biodiversity. Fungal Diversity 4:53-73

Kjer J, Debbab A, Aly AH, Proksch P (2010). Methods for isolation of marine-derived endophytic fungi and their bioactive secondary products. Nature Protocols 5:479-490.

Küppers L, Ebrahim W, El-Neketi M, Özkaya FC, Mándi A, Kurtán T, … Proksch P (2017). Lactones from the Sponge-Derived Fungus Talaromyces rugulosus. Marine Drugs 15(11):359.

Li S, Wei M, Chen G, Lin Y (2012). Two new dihydroisocoumarins from the endophytic fungus Aspergillus sp. collected from the South China Sea. Chemistry of Natural Compounds 48:371-373.

Liu DS, Huang YL, Ma LY, Lu CJ, Liu WZ (2016). Chemical constituents and their cytotoxic activities of the secondary metabolites of Penicillium janthinellum. Chinese Traditional Patent Medicine 38:830-834.

Liu Y, Kurtán T, Yun WC, Han LW, Orfali R, Müller WE, Daletos G, Proksch P (2016). Cladosporinone, a new viriditoxin derivative from the hypersaline lake derived fungus Cladosporium cladosporioides. The Journal of Antibiotics 69(9):702-706.

Lu YY, Zhang JL, Qian JM (2008). The effect of emodin on VEGF receptors in human colon cancer cells. Cancer Biotherapy & Radiopharmaceuticals 23(2):222-228.

Luo XW, Gao CH, Han FH, Chen XQ, Lin XP, Zhou XF, Wang JJ, Liu YH (2019). A new naphthopyranone from the sponge‐associated fungus Penicillium sp. XWS02F62. Magnetic Resonance in Chemistry 57(11):982-986.

Ma Y, Galinski EA, Grant WD, Oren A, Ventosa A (2010). Halophiles 2010: life in saline environments. Applied and Environmental Microbiology 76:6971-6981.

Matsuda Y, Abe I (2016). Biosynthesis of fungal meroterpenoids. Natural Product Reports 33(1):26-53.

Meier D, Hernández MV, van Geelen L, Muharini R, Proksch P, Bandow JE, Kalscheuer R (2019). The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria. Bioorganic & Medicinal Chemistry 27(23):115151.

Moussa M, Ebrahim W, Kalscheuer R, Liu Z, Proksch P (2020). Co-culture of the bacterium Pseudomonas aeruginosa with the fungus Fusarium tricinctum induces bacterial antifungal and quorum sensing signaling molecules. Phytochemistry Letters 36:37-41.

Moussa M, Ebrahim W, Bonus M, Gohlke H, Mándi A, Kurtán T, Hartmann R, Kalscheuer R, Lin W, Liu Z, Proksch P (2019). Co-culture of the fungus Fusarium tricinctum with Streptomyces lividans induces production of cryptic naphthoquinone dimmers. RSC Advances 9:1491-1500.

Nagashima H, Nakamura K, Gota T (2002). Possible anti-atherogenic effects of emodin, an anthraquinone from Chinese herbs and Aspergillus and Penicillium fungi. Mycotoxins 52(1):23-27.

Nakano H, Komiya T, Shibata S (1972). Anthraquinones of the lichens of Xanthoria and Caloplaca and their cultivated mycobionts. Phytochemistry 12:3505-3508.

Ngan NTT, Quang TH, Kim KW, Kim HJ, Sohn JH, Kang DG, Lee HS, Kim Y, Oh H (2017). Anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungal strain Penicillium sp. SF-5629. Archives of Pharmacal Research 40:328-337.

Nielsen KF, Dalsgaard PW, Smedsgaard J, Larsen TO (2005). Andrastins A−D, Penicillium roqueforti metabolites consistently produced in blue-mold-ripened cheese. Journal of Agricultural and Food Chemistry 53(8):2908-2913.

O'Brien M, Nielsen KF, O'Kiely P, Forristal PD, Fuller HT, Frisvad JC (2006). Mycotoxins and other secondary metabolites produced in vitro by Penicillium paneum Frisvad and Penicillium roqueforti Thom isolated from baled grass silage in Ireland. Journal of Agricultural and Food Chemistry 54:9268-9276.

Overy DP, Larsen TO, Dalsgaard PW, Frydenvang K, Phipps R, Munro MHG, Christophersen C (2005). Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium albocoremium: chemotaxonomic significance and pathological implications. Mycological Research 109(11):1243-1249.

Qi J, Shao CL, Li ZY, Gan LS, Fu XM, Bian WT, … Wang CY (2013). Isocoumarin derivatives and benzofurans from a sponge-derived Penicillium sp. fungus. Journal of Natural Products 76(4):571-579.

Reio L (1959). A method for the paper-chromatographic separation and identification of phenol derivatives, mould metabolites and related compounds of biochemical interest, using a “reference system”. Chromatographic Reviews 1:39-74.

Rojas-Aedo JF, Gil-Durán C, Goity A, Vaca I, Levicán G, Larrondo LF, Chávez R (2018). The developmental regulator Pcz1 affects the production of secondary metabolites in the filamentous fungus Penicillium roqueforti. Microbiological Research 212-213:67-74.

Satyanarayana T, Raghukumar C, Shivaji S (2005). Extremophilic microbes: diversity and perspectives. Current Science 89:78-90.

Sheng J, Liu D, Jing L, Xia G, Zhang W, Jiang J, Tang J (2019). Striatisporolide A, a butenolide metabolite from Athyrium multidentatum (Doll.) Ching, as a potential antibacterial agent. Molecular Medicine Reports 20:198-204.

Stewart M, Capon RJ, Lacey E, Tennant S, Gill JH (2005). Calbistrin E and two other new metabolites from an Australian isolate of Penicillium striatisporum. Journal of Natural Products 68(4):581-584.

Uchida R, Shiomi K, Inokoshi J, Sunazuka T, Tanaka H, Iwai Y, Takayanagi H, Omura S (1996). Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. II. Structure elucidation and biosynthesis. The Journal of Antibiotics 49(5):418‐424.

Wang PL, Li DY, Xie LR, Wu X, Hua HM, Li ZL (2014). Two new compounds from a marine-derived fungus Penicillium oxalicum. Natural Products Research 28:290-293.

Wilson ZE, Brimble MA (2009). Molecules derived from the extremes of life. Natural Products Reports 26:44-71

Yadav AN, Verma P, Kumar V, Sangwan P, Mishra S, Panjiar N, Gupta VK, Saxena AK (2018). Biodiversity of the Genus Penicillium in Different Habitats. In: Gupta VK, Rodriguez-Couto S (Eds). New and Future Developments in Microbial Biotechnology and Bioengineering: Penicillium System Properties and Applications. Elsevier pp 3-18.

Yadav JS, Mishra AK, Dachavaram SS, Kumar SG, Das S (2014). First enantioselective total synthesis of penicimarin B, aspergillumarins A and B. Tetrahedron Letters 55(18):2921-2923

Zhang CL, Zheng BQ, Lao JP, Mao LJ, Chen SY, Kubicek CP, Lin FC (2008). Clavatol and patulin formation as the antagonistic principle of Aspergillus clavatonanicus, an endophytic fungus of Taxus mairei. Applied Microbiology and Biotechnology 78:833-840.




How to Cite

EZE, P. M. ., GAO, Y., LIU, Y., van GEELEN, L., EJIKEUGWU, C. P., ESIMONE, C. O., OKOYE, F. B. C., PROKSCH, P., & KALSCHEUER, R. (2021). Secondary metabolites of a marine-derived Penicillium ochrochloron. Notulae Scientia Biologicae, 13(3), 11020.



Research articles
DOI: 10.15835/nsb13311020