MARINE FUNGI Understanding the biology of marine fungi for the production of secondary metabolites to establish a natural product library

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1 MARINE FUNGI Understanding the biology of marine fungi for the production of secondary metabolites to establish a natural product library Dr. Antje Labes

2 Helmholtz Center for Ocean Research Kiel Marine microbial compounds: from habitat to product Kiel Center for marine natural compounds

3 Marine Biotechnology: First Achievements Yondelis Anti-Cancer drug PharmaMar Tunicate Collagen wound gel CRM Jellyfish R&D stage New antibiotics for treatment R&D stage NIVEA Q10 plus Face cream Beiersdorf Macroalgae Magnum Ice cream Unilever Fish 7 compounds on the market Concentrate Feeding stuff Blue Biotech GmbH Microalgae New microbial strains for degradation of pollutants R&D stage Bio-kerosine Airbus Microalgae R&D stage Anti-fouling substance LimnoMar R&D stage New techniques and methods sufficient for the exploitation of marine organisms R&D stage Quelle: SUBMARINER

4 Marine Fungi represent an excellent source for new bioactives Newmann & Cragg 2009, Imhoff et al. 2011,

5 From ecology to biotechnology? Diversity and potential of marine organisms Ecologically sound and sustainable production for various fields of application in human medicine, healthy food, novel feed, environmental protection etc. Understanding biology and interaction

6 Sampling campaigns: macrobes as microhabitats 6

7 Fungal biodiversity in a sponge Wiese et al. 2011

8 Isolates Pure cultures conservation chemical screening + bioactivities morphology Molecular identification 2

9 Marine habitat Isolation Strains Novel isolation strategies Strain collections Genomic approaches Cultivation and extraction Modification of growth parameters* Strain optimization Extracts Purification Bioactivity Compounds Structure elucidation Pure compound library Bioassays Structures Selection Bioactivity Process development Imhoff et al Lead structure development

10 Raw extract Analytical HPLC Preparative HPLC Library Storage of the pure compounds P6 P7 NO Purity > 80%? YES Database & literature search Structure elucidation Bioassays Compounds already in Library? YES NO

11 Calcarisporium sp. KF525 2 µm Photo: Rolf Schmaljohann 1 µm Photo: Rolf Schmaljohann Cultivation in four different media

12 Czapek medium Casamino acids glucose medium Potato-carrot medium Modified Wickerham medium

13 Calcarisporium sp. on Casamino acids medium antibiotics of typ 15G256 Cyclodepsipeptides

14 Calcarides Methyl-15G256α Methyl-15G256β Methyl-15G256α-1 Methyl-15G256α-2 Silber et al. 2012

15 Calcaripeptides Acremolid A Ratnayake et al Silber et al

16 Scaling as a task for sustainable supply: MF458 4,00E , Production Malettinin B (TIC) 3,00E+008 2,00E+008 1,00E po2 (%) 5,0 ph 4, C ,00E ,0 0 Time (h)

17 Library construction habitat screening strain identification fermentation extraction purification physicochemical properties bioactivities literature strain collection information stored items stored compound collection linking the microorganism with the compound and the compound with its activity.

18 Marine habitat Isolation Strains Novel isolation strategies Strain collections Genomic approaches Cultivation and extraction Modification of growth parameters* Strain optimization Extracts Purification Bioactivity Compounds Structure elucidation Pure compound library Bioassays Structures Selection Bioactivity Process development Imhoff et al. 2011, Lead structure ELRIG Research & Innovation 2014 Schneemann impact into et cancer al development

19 OH H 3 C CH 3 O Teknologisk Institut H 2 C N NNH O H 3 C O N H N 11 partners, 7 countries

20 Much of nature s treasure trove of small molecules remains to be explored, particularly from the marine and microbial environments. (Newman & Cragg, 2007)