Tryptophan triggers the production of anthranilamide and quinazolinone derivatives in Streptomyces sp. PC4-3.

Streptomycetes are a valuable source of bioactive compounds, yet their biosynthetic diversity is often limited in laboratory conditions. The one strain-many compounds (OSMAC) strategy has been used to trigger the production of diverse microbial metabolites. In the present work, we observed an increased production of anthranilamide derivatives in a culture of Streptomyces sp. PC4-3 when supplemented with l-tryptophan. Three new natural products-streptotryptophin A (1), trans-streptotryptophin B (2), and cis-streptotryptophin B (3), together with three known compounds including 2,3-dihydro-2,2-dimethylquinazolin-4(1H)-one (4), nocardamine (5), and geldanamycin (6), were isolated from the tryptophan-supplemented Streptomyces culture. Structure elucidation of the isolated compounds was performed by analysis of NMR and MS data, as well as by single-crystal X-ray analysis. Compounds 2 and 3 are new natural products, and the trans and cis configurations of 2 and 3 have never been reported. We conclusively established the trans and cis configurations of 2 and 3 by single-crystal X-ray analysis, and proposed a biosynthetic pathway for compounds 1-3. A large amount (389.8 mg) of the trans isomer 2 was obtained when compared to the cis isomer 3 (15.2 mg). To our knowledge, this is the first report on the production of compounds 1-3 in nature, which is stimulated by an amino acid tryptophan. The isolated compounds did not exhibit antiviral activity against SARS-CoV-2, however, nocardamine (5) and geldanamycin (6) had antibacterial activity.