Biosynthetic Study of Amphidinin A and Amphidinolide P

Abstract

The biogenetic origins of amphidinin A (1) and amphidinolide P (2) were investigated by feeding experiments with 13 C-labeled acetates. 13 C-NMR data of 13 C-enriched samples revealed that the all carbons of 1 and 2 were derived from acetates. The polyketide chain of 1 was formed from one triketide chain, two diketide chains, and three unusual isolated C 1 units derived from C-2 of cleaved acetates, while the polyketide chain of 2 was formed from one pentaketide chain, two acetate units, and three unusual isolated C 1 units derived from C-2 of cleaved acetates. The all branched C 1 units of 1 and 2 were derived from C-2 of cleaved acetates.Key words marine dinoflagellate; Amphidinium sp.; polyketide; biosynthesis; amphidinin A; amphidinolide P Marine dinoflagellate has been recognized as the organism produce novel secondary metabolites with intriguing structures and significant biological activities.1) In our continuing search for bioactive metabolites from marine dinoflagellates, we have isolated a series of macrolides, amphidinolides, and linear polyketides from symbiotic dinoflagellates belonging to the genus Amphidinium.2-7) The carbon skeletons of dinoflagellate polyketides are unique and unavailable from other organisms, since they might be generated by unexplained one-carbon extension machinery in addition to the ordinary polyketide biosynthesis. 8) In our continuing biosynthetic study of dinoflagellate polyketides, 9-16) we have recently re-isolated amphidinin A (1) 17,18) and amphidinolide P (2) 19,20) from the cultured marine dinoflagellate Amphidinium sp. (2012-7-4A strain) which were isolated from an acoel flatworm Amphiscolops sp. In this study, we have investigated the biogenetic origins of 1 and 2 by feeding experiments with [1- Though all carbons were enriched in some measure by 13C labeled carbon dioxides generated by the metabolism of

Potent Cytotoxic Analogs of Amphidinolides from the Atlantic Octocoral Stragulum bicolor

“…It has also been proposed that small (15- and 16-membered) and large (26-membered) macrocycles target actin-G or actin-F alternatively. Together with similar macrolides reported with other names (amphidinolactones, iriomoteolides and caribenolide I) [9,10,11,12,13] and related linear polyketides (e.g., amphidinins) [14,15,16,17], AMPs are produced by dinoflagellates of the genus Amphidinium . Recently, we have reported the extraction of a number of amphidinolides from the softcoral Stragulum bicolor [18,19], including the known amphidinolide P and T1 and three new analogues named amphidinolide C4, B8 and B9 according to the structural relationship with other known members of the family.…”

“…We did not carry out any biosynthetic study on 1 – 4 in S. bicolor . However, their biogenesis could be related to that of amphidinolide P from Amphidinium sp., as described by the group of Prof. Kobayashi [15].…”

Integrated omics unveil the secondary metabolic landscape of a basal dinoflagellate

“…Glycine is incorporated into complex metabolites in the Symbiodiniaceae by bridging and forming hybrid molecules, such as zooxanthellatoxin B (ZT-B) and zooxanthellamide D (ZAD-D) [ 30 , 31 ]; however, none of the amphidinolides and related polyketides [ 17 , 32 ] isolated from A. gibbosum (amphidinin A and amphidinolide P) contains glycine, resulting in smaller, simpler molecules. Marine dinoflagellates synthesize polyketides that are usually polyol in nature [ 33 ].…”

Marine natural products

“…The polyketide chain of amphidinin A was formed from one triketide and two diketide chains and three unusual isolated C1 units derived from C-2 of cleaved acetates, while the polyketide chain of amphidinolide P was formed from one pentaketide chain, two acetate units, and three isolated C1 units also derived from C-2 of cleaved acetates. 311 Feeding of 15 N-labelled intermediates into paralytic shellsh toxins (PSTs) in Alexandrium circinalis indicated that biosynthetic intermediates predicted from gene sequences are genuine precursors of PSTs and that a related compound derived from one of these precursors is a shunt product released from cells to reduce PST production. 312…”