A recently reported incorrect structure revision and assignment of guanitrypmycins raised our attention and encouraged us to clarify the disagreement with additional experimental data. Genome mining of Kitasatospora azatica revealed the presence of a biosynthetic gene cluster for guanitrypmycin-type alkaloids. Expression of this silent cluster in Streptomyces albus led to the identification of two cyclo-l-Trp-l-Trp (1) adducts with guanine (2a and 2b) and two with hypoxanthine (3a and 3b). Detailed NMR analysis and comparison with the published data proved that compound 2a, which was misassigned to guanitrypmycin C3-1 with an N1-C8' connection in a previous report, corresponds to guanitrypmycin D3 with a C2-C8' connection, obtained by a precursor-directed biotransformation. The NMR data of 3b differ clearly from those of guanitrypmycin C3-4 with a C3-C2' connection published in 2019 and correspond very well to those of an allegedly revised guanitrypmycin C3-4 with a C3-C8' connection published in 2024. We therefore corrected this revision and named 3b guanitrypmycin C3-5.
Mann et al. (Tue,) studied this question.