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Aldsulfin, a novel unusual anti-mannheimiosis epithiodiketopiperazine antibiotic produced by Lasiodiplodia pseudotheobromae FKI-4499

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Abstract

An anti-mannheimiosis agent, aldsulfin, was isolated from a culture broth of the fungus Lasiodiplodia pseudotheobromae FKI-4499, together with a known compound, lasiodipline C, using bioassay-guided fractionation. Spectroscopic analysis of aldsulfin, using NMR, mass spectrometry, and CD analyses revealed it to be an epithiodiketopiperazine with an unstable and unusual hemithioaminal moiety. Aldsulfin showed antibacterial activity against Mannheimia haemolytica and Pasteurella multocida.

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Acknowledgements

We are grateful to Dr. Kenichiro Nagai and Noriko Sato, School of Pharmacy, Kitasato University for measurements of mass and NMR spectra. Dr. Aoi Kimishima for giving me the knowledge of organic chemistry. We sincerely thank Dr. Yoshihiro Shimizu, Dr. Osamu Yoshida, and Dr. Robert L. Harris, Animal Health Division, Eli Lilly Inc. (separated as Elanco Animal Health Inc.) for valuable help on this screening program. This study was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP19am0101096.

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Authors and Affiliations

  1. Ōmura Satoshi Memorial Institute, Kitasato University, Tokyo, Japan

    Kazunari Sakai, Masato Iwatsuki, Yukihiro Asami, Kenichi Nonaka, Rokuro Masuma, Takuji Nakashima, Toshiyuki Tokiwa, Kazuro Shiomi & Satoshi Ōmura

  2. Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan

    Masato Iwatsuki, Masato Iizuka, Yukihiro Asami, Kenichi Nonaka, Rokuro Masuma, Mami Takizawa & Kazuro Shiomi

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  1. Kazunari Sakai
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  2. Masato Iwatsuki
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Correspondence to Masato Iwatsuki.

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Sakai, K., Iwatsuki, M., Iizuka, M. et al. Aldsulfin, a novel unusual anti-mannheimiosis epithiodiketopiperazine antibiotic produced by Lasiodiplodia pseudotheobromae FKI-4499. J Antibiot 74, 363–369 (2021). https://doi.org/10.1038/s41429-021-00411-8

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