Insights into phosphatase-activated chemical defense in a marine sponge holobiont

Takahiro Jomori; Kenichi Matsuda; Yoko Egami; Ikuro Abe; Akira Takai; Toshiyuki Wakimoto

doi:10.1039/d1cb00163a

Insights into phosphatase-activated chemical defense in a marine sponge holobiont

RSC Chem Biol. 2021 Oct 6;2(6):1600-1607. doi: 10.1039/d1cb00163a. eCollection 2021 Dec 2.

Authors

Takahiro Jomori¹, Kenichi Matsuda^{1

2}, Yoko Egami¹, Ikuro Abe^{3

4}, Akira Takai⁵, Toshiyuki Wakimoto^{1

2}

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6 Sapporo 060-0812 Japan.
² Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Kita 12, Nishi 6 Sapporo 060-0812 Japan.
³ Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033 Japan.
⁴ Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku Tokyo 113-8657 Japan.
⁵ Department of Physiology, Asahikawa Medical University, 1-1-1 Midorigaoka Higashi 2 jo Asahikawa 078-8510 Japan.

Abstract

Marine sponges often contain potent cytotoxic compounds, which in turn evokes the principle question of how marine sponges avoid self-toxicity. In a marine sponge Discodermia calyx, the highly toxic calyculin A is detoxified by the phosphorylation, which is catalyzed by the phosphotransferase CalQ of a producer symbiont, "Candidatus Entotheonella" sp. Here we show the activating mechanism to dephosphorylate the stored phosphocalyculin A protoxin. The phosphatase specific to phosphocalyculin A is CalL, which is also encoded in the calyculin biosynthetic gene cluster. CalL represents a new clade and unprecedently coordinates the heteronuclear metals Cu and Zn. CalL is localized in the periplasmic space of the sponge symbiont, where it is ready for the on-demand production of calyculin A in response to sponge tissue disruption.