Cryptic Biosynthesis of the Berkeleypenostatins from Coculture of Extremophilic Penicillium sp

J Nat Prod. 2021 May 28;84(5):1656-1665. doi: 10.1021/acs.jnatprod.1c00248. Epub 2021 May 6.

Abstract

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 μM 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Biological Products / metabolism
  • Biological Products / pharmacology
  • Cell Line, Tumor
  • Citrinin
  • Coculture Techniques
  • Extremophiles / chemistry
  • Humans
  • Macrolides
  • Molecular Structure
  • Patulin
  • Penicillium / chemistry*

Substances

  • Antineoplastic Agents
  • Biological Products
  • Macrolides
  • Citrinin
  • Patulin

Supplementary concepts

  • Penicillium camemberti
  • Penicillium clavigerum
  • Penicillium fuscum