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

Muslimin Rukman

Ali Alimuddin

Ogaki Sho

Nurjannah

Alam Ummu Kalsum

Choi Sisun

Kim Eung-Soo

Arakawa Kenji

Tetrahedron

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 ester-bond 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.

Endophytic streptomyces

Sulawesi island

Macrotetrolides

Hydrolysis

Seco-acids

英語

Elsevier

© 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

This is not the published version. Please cite only the published version.

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[DOI] https://doi.org/10.1016/j.tet.2024.134045 ～の異版である

日本学術振興会

Japan Society for the Promotion of Science

[Crossref Funder] https://doi.org/10.13039/501100001691

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Elucidation of molecular basis of Streptomyces signaling-molecule-dependent regulatory pathway and activation of silent secondary metabolite biosynthetic genes

22H02274

日本学術振興会

Japan Society for the Promotion of Science

[Crossref Funder] https://doi.org/10.13039/501100001691

多様な生態系を創出するインドネシア・スラウェシ島の天然資源調査と徹底的利活用

Exploring and extensive utilization of natural products in Sulawesi Island, Indonesia, creating the ecosystem diversity

19KK0149