Cyclodipeptide synthases (CDPSs) can catalyze the formation of two successive peptide bonds by hijacking aminoacyl-tRNAs from the ribosomal machinery resulting in diketopiperazines (DKPs). Here, three CDPS-containing loci (dmt1–3) are discovered by genome mining and comparative genome analysis of Streptomyces strains. Among them, CDPS DmtB1, encoded by the gene of dmt1 locus, can synthesize cyclo(L-Trp-L-Xaa) (with Xaa being Val, Pro, Leu, Ile, or Ala). Systematic mutagenesis experiments demonstrate the importance of the residues constituting substrate-binding pocket P1 for the incorporation of the second aa-tRNA in DmtB1. Characterization of dmt1–3 unravels that CDPS-dependent machinery is involved in CDPS-synthesized DKP formation followed by tailoring steps of prenylation and cyclization to afford terpenylated DKP compounds drimentines. A phytoene-synthase-like family prenyltransferase (DmtC1) and a membrane terpene cyclase (DmtA1) are required for drimentines biosynthesis. These results set the foundation for further increasing the natural diversity of complex DKP derivatives.
Indotertine A (1), a hybrid isoprenoid with a condensed pentacyclic skeleton, together with two related hybrid isoprenoids, drimentines F (2) and G (3), were isolated from a reeds rhizosphere soil derived actinomycete Streptomyces sp. CHQ-64. Their structures including absolute configurations were elucidated by spectroscopic methods, X-ray single crystal diffraction analysis, and TDDFT ECD calculations. Drimentines G (3) showed strong cytotoxicity against human cancer cells lines with IC(50)'s down to 1.01 μM, while 1 and 2 showed no significant activity.
Six new epipolythiodioxopiperazine (ETP) alkaloids, penicisulfuranols A-F (1-6), were isolated from the mangrove endophytic fungus Penicillium janthinellum HDN13-309. All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data and ECD calculations. They belong to the unusual family of ETPs containing sulfur atoms on both α- and β-positions of amino acid residues and a rare 1,2-oxazadecaline core moiety. In addition, compounds 1-6 also possess a rare spiro-furan ring and 1-3 showed cytotoxicity with IC values ranging from 0.1 to 3.9 μM.
Four new alkyl aromatics, penixylarins
A–D (1–4), along with the
known biogenetically related
1,3-dihydroxy-5-(12-hydroxyheptadecyl)benzene (5) and
1,3-dihydroxy-5-(12-sulfoxyheptadecyl)benzene (6), were
isolated from a mixed culture of the Antarctic deep-sea-derived fungus Penicillium crustosum PRB-2 and the mangrove-derived fungus Xylaria sp. HDN13-249. UPLC-MS data and an analysis of structural
features showed that compounds 1 and 2 were
produced by collaboration of the two fungi, while compounds 3–6 could be produced by Xylaria sp. HDN13-249 alone, but in noticeably increased quantities by cocultivation.
Compounds 2, 3, 5, and 6 showed antibacterial activity against a panel of strains,
and compound 3 possessed potential antituberculosis effects
(MIC = 6.25 μM against Mycobacterium phlei).
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