Biotransformation of cladribine by a nanostabilized extremophilic biocatalyst

J Biotechnol. 2020 Nov 10:323:166-173. doi: 10.1016/j.jbiotec.2020.08.012. Epub 2020 Aug 22.

Abstract

Cladribine (2-chloro-2'-deoxy-β-d-adenosine) is a 2'-deoxyadenosine analogue, approved by the FDA for the treatment of hairy cell leukemia and more recently has been proved for therapeutic against many autoimmune diseases as multiple sclerosis. The biosynthesis of this compound using Thermomonospora alba CECT 3324 as biocatalyst is herein reported. This thermophilic microorganism was successfully entrapped in polyacrylamide gel supplemented with nanoclays such as bentonite. The immobilized biocatalyst (T. alba-Ac-Bent 1.00 %), was able to biosynthesize cladribine with a conversion of 89 % in 1 h of reaction and retains its activity for more than 270 reuses without significantly activity loss, showing better operational stability and mechanical properties than the natural matrix. A microscale assay using the developed system, could allow the production of at least 181 mg of cladribine in successive bioprocesses.

Keywords: Antileukemic agent; Nanocomposites; Polyacrylamide; Thermophilic biocatalyst.

MeSH terms

  • Acrylic Resins
  • Antineoplastic Agents / therapeutic use
  • Biosynthetic Pathways
  • Biotransformation*
  • Cladribine / metabolism*
  • Cladribine / therapeutic use
  • Deoxyadenosines
  • Extremophiles / physiology*
  • Geobacillus
  • Leukemia, Hairy Cell / drug therapy
  • Nanocomposites
  • Temperature
  • Thermobifida / growth & development
  • Thermobifida / metabolism

Substances

  • Acrylic Resins
  • Antineoplastic Agents
  • Deoxyadenosines
  • Cladribine
  • polyacrylamide
  • 2'-deoxyadenosine

Supplementary concepts

  • Thermobifida alba