Detection of seco-macrotetrolides caused by regiospecific hydrolysis in Indonesian Streptomyces strains isolated at the karst area in Sulawesi Island

초록

Among a total of 30 endophytic Streptomyces strains collected at the karst area in Sulawesi Island, Indonesia, four strains showed antimicrobial activity together with distinct purple-colored spot(s) on TLC after anisaldehyde staining and baking. Four endophytic strains AA004, AA010, AA034, and AA035 accumulated ionophore macrotetrolides (cyclic tetraesters) including nonactin, monactin, dinactin, trinactin, and tetranactin. Occasionally, strains AA034 and AA035 accumulated considerable amount of seco-macrotetrolides (ring-opened, linear macrotetrolides) including seco-dinactin, seco-monactin, and seco-trinactin, together with macrotetrolides as above mentioned. Time-course increase of seco-macrotetrolides indicates the subsequent hydrolysis of macrotetrolides. Seco-macrotetrolides in strain AA034 were separated from macrotetrolides and other metabolites through Sephadex LH20 and silica gel chromatographies, although seco-macrotetrolides contain inseparable five analogs. We here investigated the hydrolyzed positions in seco-macrotetrolides. ESI-CID-MS/MS analysis of seco-dinactin (m/z 805 as [M+Na]+) and its derivatives, methyl ester (m/z 819 as [M+Na]+) and O-acetyl methyl ester (m/z 861 as [M+Na]+), revealed that seco-dinactin obtained in strains AA034/AA035 is a single regioisomer with a cleavage at an ester bond between the alcohol of (-)-homononactate and the carboxylate of (+)-nonactate, suggesting the regioselective hydrolysis on the occurrence of seco-dinactin. Further ESI-CID-MS/MS analysis revealed that seco-monactin (m/z 791 as [M+Na]+) is also single regioisomer with the ester-bond cleavage between the alcohol of (-)-homononactate and the carboxylate of (+)-nonactate. In the case of seco-trinactin (m/ z 819 as [M+Na]+), additional regioisomer with the ester-bond cleavage between the alcohol of (-)-homononactate and the carboxylate of (+)-homononactate was detected, together with the regioisomer with the esterbond cleavage between the alcohol of (-)-homononactate and the carboxylate of (+)-nonactate. A mixture of seco-macrotetrolides exhibited no antimicrobial activity, indicating the importance of macrocyclic structure for antimicrobial activity.

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