30 HML, a new anti-red tide compound produced by marine bacteria
Details
The harmful dinoflagellate Heterocapsa circularisquama has caused large-scale red tides in the coastal embayments of central and western Japan. Red tides of H. circularisquama have been responsible for mass mortalities of both natural and cultured bivalves such as pearl oyster, and short-necked clam and oyster. HML (Hydorxy Myristoyl Leucine), a novel compound was found as a promising agent through screening of 5,000 marine bacterial broth extractions. HML(1) showed crucial activity against H. circularisquama and Prorocentrum micans. On the other hand it showed less algicidal activity against the diatom, Skeletonema costaum or Cheatoceros decipiens which are the main foods for shellfishes. In order to enhancement of this selective algicidal effect, more than 40 analogues of HML(1) have been chemically synthesized. Nevertheless the algicidal mechanism of HML have not been clarified, some information about structure-activity correlation was obtained. Stereochemistries of HML(1) were determined to [3(S), 2(R)] by the comparison of chemically synthesized all four possible steroisomers. HML and its enantiomer analogue [3(S), 2'(R)] (2) have algicidal effect for dinofllagellate but not for diatom,. while [3(S), 2'(S)](3), [3(R), 2'(R)] or (4) analogue lacks of selective effect and have some algicidal acictity against diatom. Chain-length of HML is essential for the intense of activity, and longer or shorter analogue on fatty acid moiety, decrease the algicidal activity. Analogues of modified carboxylic acid, such as methyl ester or amide, drastically decreased the acitivity. Enhancement of acitiviy was achieved by the replacement of leucine with aspartic acid and this most potent synthetic analogue HMAsp 6) can terminate H. circularisquam at 0.3mg/L for 4 hours.
