Jomori Takahiro, Matsuda Kenichi, Egami Yoko, Abe Ikuro, Takai Akira, Wakimoto Toshiyuki
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6 Sapporo 060-0812 Japan.
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.
RSC Chem Biol. 2021 Oct 6;2(6):1600-1607. doi: 10.1039/d1cb00163a. eCollection 2021 Dec 2.
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 , the highly toxic calyculin A is detoxified by the phosphorylation, which is catalyzed by the phosphotransferase CalQ of a producer symbiont, " 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.
海洋海绵通常含有强效细胞毒性化合物，这进而引发了一个主要问题，即海洋海绵如何避免自身中毒。在一种海洋海绵中，剧毒的calyculin A通过磷酸化作用解毒，该磷酸化反应由共生生产者“Entotheonella”属的磷酸转移酶CalQ催化。在此，我们展示了使储存的磷酸化calyculin A原毒素去磷酸化的激活机制。对calyculin A具有特异性的磷酸酶是CalL，它也编码于calyculin生物合成基因簇中。CalL代表一个新的进化枝，并且以前所未有的方式协调异核金属铜和锌。CalL定位于海绵共生体的周质空间，在那里它随时准备在海绵组织受到破坏时按需产生calyculin A。
