Metabolism of natural and synthetic bioactive compounds in Cunninghamella fungi and their applications in drug discovery

Bioorg Chem. 2023 Nov:140:106801. doi: 10.1016/j.bioorg.2023.106801. Epub 2023 Aug 23.

Abstract

Investigation of xenobiotic metabolism is a key step for drug discovery. Since the in vivo investigations may be associated with harmful effects attributed to production of toxic metabolites, it is deemed necessary to predict their structure especially at the preliminary clinical studies. Furthermore, the application of microorganisms that are capable of metabolizing drugs mimic human metabolism and consequently may predict possible metabolites. The genus Cunninghamella has been proven to be a potential candidate, which mimics xenobiotic metabolism occurring inside the human body, including phase I and II metabolic reactions. Moreover, biotransformation with Cunninghamella showed chemical diversity, where a lot of products were detected in relation to the initial substrates after being modified by oxidation, hydroxylation, and conjugation reactions. Some of these products are more bioactive than the parent compounds. The current review presents a comprehensive literature overview regarding the Cunninghamella organisms as biocatalysts, which simulate mammalian metabolism of natural secondary and synthetic compounds.

Keywords: Biocatalysis; Biotransformation; Cunninghamella; Metabolism; Secondary metabolites.

Publication types

  • Review

MeSH terms

  • Animals
  • Cunninghamella*
  • Drug Discovery
  • Humans
  • Hydroxylation
  • Mammals
  • Xenobiotics

Substances

  • Xenobiotics