A one-pot/two-stage precursor-directed biosynthesis approach was used to introduce selected sulfanilamide derivatives into the talaroenamine pathway in a Yellow River wetland-derived fungus. During this approach, precursors p -methylaniline and sulfanilamide derivatives were added to the medium in two stages, improving the substrate acceptance of biosynthetic intermediate cyclohexanedione to form diverse talaroenamines. Ten new sulfa-containing talaroenamine derivatives, sulfarulumines A-J ( 1 – 10 ), were isolated and structurally characterized. Compound 2 displayed acetylcholinesterase (AChE) inhibitory effect with an IC 50 value of 4.9 µM. Molecular docking study suggested that 2 exerted inhibitory activity by binding to an active site of the enzyme.
Precursor-directed biosynthesis was used to introduce selected aniline derivatives into the talaroenamine pathway, which had recently been defined from a Yellow River wetland-derived Penicillim malacosphaerulum HPU-J01. The known talaroenamine B (1) and six previously undescribed talaroenamine derivatives, talaroenamines F–K (2–7), were generated and structurally characterized. The aniline derivatives are introduced via nonenzymatic addition to the reactive intermediate cyclohexanedione. Compound 2 was active against Bacillus cereus with an MIC value of 0.85 μg/mL.
Nineteen new talaroenamine derivatives, talaroenamines F1–F19 (1–19), were isolated from the Yellow River wetland derived Penicillium malacosphaerulum HPU-J01 by use of a one-pot/two-stage precursor-directed biosynthesis approach. During this approach, the initial precursor p-methylaniline was first used as a carrier to capture the biologically synthesized cyclohexanedione to produce talaroenamine F, and then the other aniline derivatives were employed to replace the p-methylaniline fragment of talaroenamine F to generate the final products. LC–MS analysis showed that only four compounds (2, 8, 10, and 12) could be produced by the traditional precursor-directed biosynthesis in which the aniline precursors were added simultaneously. Compound 14 was cytotoxic against the K562 cell line with an IC50 value of 2.2 μM. This work demonstrated the one-pot/two-stage precursor-directed biosynthesis could improve substrate acceptance leading to the production of diverse talaroenamines.
危险品化学品经营许可证（带存储）