Cryptic Biosynthesis of the Berkeleypenostatins from Coculture of Extremophilic Penicillium sp.

Coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded berkeleypenostatins A-G (1-7) as well as the previously reported berkeleylactones A-H, the known macrolide A26771B, citrinin, and patulin. As was true with the berkeleylactones, there was no evidence of the berkeleypenostatins in either axenic culture. The structures were deduced from analyses of spectral data, and the absolute configuration of berkeleypenostatin A (1) was determined by single-crystal X-ray crystallography. Berkeleypenostatins A (1) and E (5) inhibited migration of human pancreatic carcinoma cells (HPAF-II). Both compounds were tested by the NCI Developmental Therapeutics Program. In the NCI 60 cell five-dose screen, berkeleypenostatin E (5) was the more active of the two, with 1-10 mu M total growth inhibition (TGI) of all leukemia cell lines, as well as the majority of colon, CNS, melanoma, ovarian, prostate, renal, and breast cancer cell lines.

Automated summary

The coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum produced berkeleypenostatins A and E, which showed significant inhibitory effects on the migration of human pancreatic carcinoma cells. The study also revealed that berkeleypenostatins exhibited a potent growth inhibition activity against a wide range of cancer cell lines in the NCI 60 cell five-dose screen.