TY - JOUR
T1 - Biosynthetic route towards saxitoxin and shunt pathway
AU - Tsuchiya, Shigeki
AU - Cho, Yuko
AU - Konoki, Keiichi
AU - Nagasawa, Kazuo
AU - Oshima, Yasukatsu
AU - Yotsu-Yamashita, Mari
N1 - Funding Information:
This work was supported by grants from the Funding Program for Next-Generation World-Leading Researchers (LS012) to M.Y.Y. and by KAKENHI Grants-in-Aid for Scientific Research to M.Y.Y. (no. 26292057) and Y.C. (no. 15K07569) from the Japan Society for the Promotion of Science (JSPS). S.T. was the recipient of a SUNBOR scholarship from the Suntory Institute for Bioorganic Research and S.T. is a research fellow of JSPS (DC2) (no. 15J00480).
Publisher Copyright:
© 2016, Nature Publishing Group. All rights reserved.
PY - 2016/2/4
Y1 - 2016/2/4
N2 - Saxitoxin, the most potent voltage-gated sodium channel blocker, is one of the paralytic shellfish toxins (PSTs) produced by cyanobacteria and dinoflagellates. Recently, putative biosynthetic genes of PSTs were reported in these microorganisms. We previously synthesized genetically predicted biosynthetic intermediates, Int-A′ and Int-C′2, and also Cyclic-C′ which was not predicted based on gene, and identified them all in the toxin-producing cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2). This study examined the incorporation of 15N-labeled intermediates into PSTs (C1 and C2) in A. circinalis (TA04). Conversions from Int-A′ to Int-C′2, from Int-C′2 to Cyclic-C′, and from Int-A′ and Int-C′2 to C1 and C2 were indicated using high resolution-LC/MS. However, Cyclic-C′ was not converted to C1 and C2 and was detected primarily in the extracellular medium. These results suggest that Int-A′ and Int-C′2 are genuine precursors of PSTs, but Int-C′2 converts partially to Cyclic-C′ which is a shunt product excreted to outside the cells. This paper provides the first direct demonstration of the biosynthetic route towards saxitoxin and a shunt pathway.
AB - Saxitoxin, the most potent voltage-gated sodium channel blocker, is one of the paralytic shellfish toxins (PSTs) produced by cyanobacteria and dinoflagellates. Recently, putative biosynthetic genes of PSTs were reported in these microorganisms. We previously synthesized genetically predicted biosynthetic intermediates, Int-A′ and Int-C′2, and also Cyclic-C′ which was not predicted based on gene, and identified them all in the toxin-producing cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2). This study examined the incorporation of 15N-labeled intermediates into PSTs (C1 and C2) in A. circinalis (TA04). Conversions from Int-A′ to Int-C′2, from Int-C′2 to Cyclic-C′, and from Int-A′ and Int-C′2 to C1 and C2 were indicated using high resolution-LC/MS. However, Cyclic-C′ was not converted to C1 and C2 and was detected primarily in the extracellular medium. These results suggest that Int-A′ and Int-C′2 are genuine precursors of PSTs, but Int-C′2 converts partially to Cyclic-C′ which is a shunt product excreted to outside the cells. This paper provides the first direct demonstration of the biosynthetic route towards saxitoxin and a shunt pathway.
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U2 - 10.1038/srep20340
DO - 10.1038/srep20340
M3 - Article
C2 - 26842222
AN - SCOPUS:84957584948
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 20340
ER -