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Ascidian-associated photosymbionts from Manado, Indonesia: secondary metabolites, bioactivity simulation, and biosynthetic insight

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Abstract

This research work aimed at investigating the chemistry and biosynthetic potential of ascidian-associated symbionts that originated from Manado Bay, North Sulawesi. We initially enriched the symbiotic cells associated with the Manadonese ascidian Lissoclinum patella. Subsequently we identified the presence of Prochloron didemni in both unenriched and salt-enriched samples by examining the 16S rRNA gene and the chlorophyll A oxygenase (CAO) gene. Investigation of the secondary metabolites by HPLC, LCMS/MS, and NMR showed the presence of ulithiacyclamide along with patellamide E in the unenriched symbiotic cells. Interestingly, ulithiacyclamide was detected in the enriched cells from the same Ascidian specimen. Molecular docking showed the high binding affinity of both compounds to estrogen receptor beta (ER-β) protein. This is a subtype of the nuclear receptor superfamily expressed abnormally in ovarian cancer cells. Furthermore, we isolated a patE gene variant encoding for a precursor with patellamide E (VTVCITFC) and ulithiacyclamide (CTLCCTLC) core peptides from the enriched cells. This represents a new core peptide combination. The outcome of this work provides a basis for producing useful cyclic peptides, in sustainable way, through symbiont cultivation. This could become a platform for bioengineering to generate diverse compound analogues.

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Acknowledgments

We thank to the Directorate of Research and Community Services, Indonesian Ministry of Research, Technology and Higher Education for financial support in 2018-2020 with a research scheme of basic priority/excellent university research (PDUPT). This work was partly supported by the Takeda Science Foundation, the Asahi Glass Foundation, the Japan Agency for Medical Research and Development (AMED Grant Number JP19ae0101045), and Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, JSPS KAKENHI (Grant Numbers JP16703511 and JP18056499). We are thankful to Adrianus Malintoi for his assistance in sample collection.

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Authors and Affiliations

  1. Faculty of Fisheries and Marine Science, Sam Ratulangi University, Manado, Indonesia

    Inneke F. M. Rumengan & Mayse S. Siby

  2. Postgraduate Program, Sam Ratulangi University, Manado, Indonesia

    Vera I. Y. Roring

  3. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    Jabal R. Haedar, Agustinus R. Uria & Toshiyuki Wakimoto

  4. Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia

    Jabal R. Haedar

  5. North Sulawesi Provincial Health Office, Manado, Indonesia

    Aldian H. Luntungan

  6. Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, Indonesia

    Beivy J. Kolondam

  7. Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan

    Agustinus R. Uria & Toshiyuki Wakimoto

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  1. Inneke F. M. Rumengan
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Rumengan, I.F.M., Roring, V.I.Y., Haedar, J.R. et al. Ascidian-associated photosymbionts from Manado, Indonesia: secondary metabolites, bioactivity simulation, and biosynthetic insight. Symbiosis 84, 71–82 (2021). https://doi.org/10.1007/s13199-021-00766-4

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