Modeling of colchicine biotransformation by COVID-19 associated Klebsiella pneumoniae: synergistic effects of cell adaptation and gamma irradiation.

BACKGROUND

Microbial biotransformation strategies for prescribed drugs have attracted great interest because the biotransformation process simulates what happens in the human metabolism and may be considered a resource for new pharmaceuticals.

METHODS

The promising candidate for colchicine biotransformation was identified using Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF/MS). Colchicine was quantified by a modified procedure based on the reduction of alkaline potassium permanganate and HPLC. Response surface methodology (RSM) was used for optimizing and modeling colchicine biotransformation. The colchicine-metabolizing products were identified using liquid chromatography-electrospray ionization-tandem mass spectrometry.

RESULTS

Fifteen bacteria infected the upper respiratory tract during the COVID-19 pandemic were collected and screened for colchicine resistance. One of them could metabolize 41.38% colchicine in enriched SF2 medium supplemented with 7gl- 1 colchicine and was identified as Klebsiella pneumoniae-4. The biotransformation of colchicine was optimized using RSM upon exposing K. pneumoniae-4 cells to gamma irradiation stress. The predictive model revealed the superiority of cell adaptation before the colchicine conversion process. The RSM optimizer showed the maximum colchicine biotransformation was achieved at variable levels: 0.41 kGy irradiation dose and 9.55 d incubation time. Chromatographic analysis showed a variation in the chemical composition of colchicine metabolized products.

CONCLUSIONS

The main colchicine metabolized products; 3-(4-hydroxyphenyl) propanoic acid, 4'-hydroxy-2'-methylacetophenone, dihydrorotenone, and glabridin, potentially could be applied in the medical field for more functions than those described for the parent compound.