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A Survey of Didemnin Depsipeptide Production in <em>Tistrella</em>
oleh: Robert J. Stankey, Don Johnson, Brendan M. Duggan, David A. Mead, James J. La Clair
Format: | Article |
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Diterbitkan: | MDPI AG 2023-01-01 |
Deskripsi
As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family <i>Didemnidae</i>, recent studies have identified their biosynthetic gene clusters from the marine–derived bacteria <i>Tistrella mobilis</i>. While these studies confirm the production of didemnin X/Y, the low titer and general lack of understanding of their biosynthesis in <i>Tistrella</i> currently prevents the development of effective microbial or synthetic biological approaches for their production. To this end, we conducted a survey of known species of <i>Tistrella</i> and report on their ability to produce the didemnin depsipeptides. These data were used to develop conditions to produce didemnin B at titers over 15 mg/L.