Conglobatins B–E: cytotoxic analogues of the C2-symmetric macrodiolide conglobatin

Heather J. Lacey*, Thomas J. Booth, Daniel Vuong, Peter J. Rutledge, Ernest Lacey, Yit Heng Chooi, Andrew M. Piggott

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)
    58 Downloads (Pure)


    Chemical investigation of a previously unreported indigenous Australian Streptomyces strain MST-91080 has identified six novel analogues related to the oxazole-pendanted macrodiolide, conglobatin. Phylogenetic analysis of the 16S rRNA gene sequence identified MST-91080 as a species of Streptomyces, distinct from reported conglobatin producer, Streptomyces conglobatus ATCC 31005. Conglobatins B–E diverge from conglobatin through differing patterns of methylation on the macrodiolide skeleton. The altered methyl positions suggest a deviation from the published biosynthetic pathway, which proposed three successive methylmalonyl-CoA extender unit additions to the conglobatin monomer. Conglobatins B1, C1 and C2 exhibited more potent cytotoxic activity selectively against the NS-1 myeloma cell line (IC50 0.084, 1.05 and 0.45 µg ml−1, respectively) compared with conglobatin (IC50 1.39 µg ml−1).

    Original languageEnglish
    Pages (from-to)756-765
    Number of pages10
    JournalJournal of Antibiotics
    Issue number11
    Early online date17 Jun 2020
    Publication statusPublished - Nov 2020


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