Alb29, an α-oxoamine synthase involved in albogrisin biosynthesis in Streptomyces albogriseolus MGR072, was characterized and responsible for the incorporation of L-glutamate to acyl-coenzyme A substrates. Combined with Alb29 and Mgr36 (an acyl-coenzyme A ligase), a one-pot enzymatic system was established to synthesize seven α-amino ketones. When these α-amino ketones were fed into the alb29 knockout strain Δalb29, respectively, the albogrisin analogs with different side chains were observed.

The known benzonaphthyridine alkaloid, albogrisin A (1), and six new compounds, including two pyrazinone stereoisomers, albogrisin B (2)/B′ (2′), together with four 4H-pyrroloquinolinones, two diastereoisomers, albogrisin C (3)/C′ (3′), and their methyl esters, albogrisin D (4)/D′ (4′), were isolated from mangrove-derived Streptomyces albogriseolus MGR072. 2 and 2′ are converted into 1 in acidic aqueous solution but into 3/3′ and 4/4′ in 0.05% trifluoroacetic acid acetonitrile. 4 and 4′ are new indoleamine 2,3-dioxygenase 1 inhibitors.

Xiamenmycin A is an antifibrotic leading compound with a benzopyran skeleton that is isolated from mangrove-derived Streptomyces xiamenensis. As a promising small molecule for fibrotic diseases, less information is known about its metabolic characteristics in vivo. In this study, the time-course of xiamenmycin A in mouse plasma was investigated by relative quantification. After two types of administration of xiamenmycin A at a single dose of 10 mg/kg, the plasma concentrations were measured quantitatively by LC-MS/MS. The dynamic changes in the xiamenmycin A concentration showed rapid absorption and quick elimination in plasma post-administration. Four metabolites (M1–M4) were identified in blood by UPLC-QTOF-MS, and xiamenmycin B (M3) is the principal metabolite in vivo, as verified by comparison of the authentic standard sample. The structures of other metabolites were identified based on the characteristics of their MS and MS/MS data. The newly identified metabolites are useful for understanding the metabolism of xiamenmycin A in vivo, aiming at the development of an anti-fibrotic drug candidate for the therapeutic treatment of excessive fibrotic diseases.