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Design of Fungal Co-Cultivation Based on Comparative Metabolomics and Bioactivity for Discovery of Marine Fungal Agrochemicals.

Identifieur interne : 000253 ( Main/Exploration ); précédent : 000252; suivant : 000254

Design of Fungal Co-Cultivation Based on Comparative Metabolomics and Bioactivity for Discovery of Marine Fungal Agrochemicals.

Auteurs : Ernest Oppong-Danquah [Allemagne] ; Paulina Budnicka [Allemagne] ; Martina Blümel [Allemagne] ; Deniz Tasdemir [Allemagne]

Source :

RBID : pubmed:31979232

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English descriptors

Abstract

Microbial co-cultivation is employed for awakening silent biosynthetic gene clusters (BGCs) to enhance chemical diversity. However, the selection of appropriate partners for co-cultivation remains a challenge. Furthermore, competitive interactions involving the suppression of BGCs or upregulation of known, functional metabolite(s) during co-cultivation efforts is also common. Herein, we performed an alternative approach for targeted selection of the best co-cultivation pair. Eight marine sediment-derived fungi were classified as strong or weak, based on their anti-phytopathogenic potency. The fungi were co-cultured systematically and analyzed for their chemical profiles and anti-phytopathogenic activity. Based on enhanced bioactivity and a significantly different metabolite profile including the appearance of a co-culture specific cluster, the co-culture of Plenodomusinfluorescens (strong) and Pyrenochaetanobilis (weak) was prioritized for chemical investigation. Large-scale co-cultivation resulted in isolation of five polyketide type compounds: two 12-membered macrolides, dendrodolide E (1) and its new analog dendrodolide N (2), as well as two rare azaphilones spiciferinone (3) and its new analog 8a-hydroxy-spiciferinone (4). A well-known bis-naphtho-γ-pyrone type mycotoxin, cephalochromin (5), whose production was specifically enhanced in the co-culture, was also isolated. Chemical structures of compounds 1-5 were elucidated by NMR, HRMS and [] analyses. Compound 5 showed the strongest anti-phytopathogenic activity against Xanthomonas campestris and Phytophthorainfestans with IC50 values of 0.9 and 1.7 µg/mL, respectively.

DOI: 10.3390/md18020073
PubMed: 31979232
PubMed Central: PMC7073616


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<term>Agrochemicals (pharmacology)</term>
<term>Aquatic Organisms (isolation & purification)</term>
<term>Aquatic Organisms (metabolism)</term>
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<term>Geologic Sediments (microbiology)</term>
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<term>Phytophthora infestans (drug effects)</term>
<term>Polyketides (isolation & purification)</term>
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<term>Produits biologiques (isolement et purification)</term>
<term>Produits biologiques (métabolisme)</term>
<term>Produits biologiques (pharmacologie)</term>
<term>Spectroscopie par résonance magnétique (MeSH)</term>
<term>Sédiments géologiques (microbiologie)</term>
<term>Techniques de coculture (méthodes)</term>
<term>Xanthomonas campestris (effets des médicaments et des substances chimiques)</term>
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<term>Sédiments géologiques</term>
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<term>Organismes aquatiques</term>
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<div type="abstract" xml:lang="en">Microbial co-cultivation is employed for awakening silent biosynthetic gene clusters (BGCs) to enhance chemical diversity. However, the selection of appropriate partners for co-cultivation remains a challenge. Furthermore, competitive interactions involving the suppression of BGCs or upregulation of known, functional metabolite(s) during co-cultivation efforts is also common. Herein, we performed an alternative approach for targeted selection of the best co-cultivation pair. Eight marine sediment-derived fungi were classified as strong or weak, based on their anti-phytopathogenic potency. The fungi were co-cultured systematically and analyzed for their chemical profiles and anti-phytopathogenic activity. Based on enhanced bioactivity and a significantly different metabolite profile including the appearance of a co-culture specific cluster, the co-culture of
<i>Plenodomus</i>
<i>influorescens</i>
(strong) and
<i>Pyrenochaeta</i>
<i>nobilis</i>
(weak) was prioritized for chemical investigation. Large-scale co-cultivation resulted in isolation of five polyketide type compounds: two 12-membered macrolides, dendrodolide E (
<b>1</b>
) and its new analog dendrodolide N (
<b>2</b>
), as well as two rare azaphilones spiciferinone (
<b>3</b>
) and its new analog 8a-hydroxy-spiciferinone (
<b>4</b>
). A well-known
<i>bis</i>
-naphtho-γ-pyrone type mycotoxin, cephalochromin (
<b>5</b>
), whose production was specifically enhanced in the co-culture, was also isolated. Chemical structures of compounds
<b>1</b>
-
<b>5</b>
were elucidated by NMR, HRMS and [] analyses. Compound
<b>5</b>
showed the strongest anti-phytopathogenic activity against
<i>Xanthomonas campestris</i>
and
<i>Phytophthora</i>
<i>infestans</i>
with IC
<sub>50</sub>
values of 0.9 and 1.7 µg/mL, respectively.</div>
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<i>Plenodomus</i>
<i>influorescens</i>
(strong) and
<i>Pyrenochaeta</i>
<i>nobilis</i>
(weak) was prioritized for chemical investigation. Large-scale co-cultivation resulted in isolation of five polyketide type compounds: two 12-membered macrolides, dendrodolide E (
<b>1</b>
) and its new analog dendrodolide N (
<b>2</b>
), as well as two rare azaphilones spiciferinone (
<b>3</b>
) and its new analog 8a-hydroxy-spiciferinone (
<b>4</b>
). A well-known
<i>bis</i>
-naphtho-γ-pyrone type mycotoxin, cephalochromin (
<b>5</b>
), whose production was specifically enhanced in the co-culture, was also isolated. Chemical structures of compounds
<b>1</b>
-
<b>5</b>
were elucidated by NMR, HRMS and [] analyses. Compound
<b>5</b>
showed the strongest anti-phytopathogenic activity against
<i>Xanthomonas campestris</i>
and
<i>Phytophthora</i>
<i>infestans</i>
with IC
<sub>50</sub>
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