Microbial cytosine deaminase is a programmable anticancer prodrug mediating enzyme: antibody, and gene directed enzyme prodrug therapy

Escherichia coli cytosine deaminase: Structural and biotechnological aspects

“…22 The bCD is primarily an intracellular enzyme, whereas the fungal CD has been reported to exist intracellularly and extracellularly. 10 From the kinetics studies of CD from different sources toward different substrates, CD from Aspergillus parasiticus and E. coli displayed the highest catalytic affinity for cytosine and 5-FC. 23 Studies on CD have primarily focused on the E. coli enzyme due to its shorter gene sequence (1.3 kb) and higher stability.…”

“…In contrast, the CD from fungal consists of two signature sequences, “HXE and CXXC,” that are conserved in deaminases and are classified under the cytidine and deoxycytidylate deaminase family 22 . The bCD is primarily an intracellular enzyme, whereas the fungal CD has been reported to exist intracellularly and extracellularly 10 . From the kinetics studies of CD from different sources toward different substrates, CD from Aspergillus parasiticus and E. coli displayed the highest catalytic affinity for cytosine and 5‐FC 23 …”

“…8,9 The CD can be found in fungi and bacteria but not mammalian cells. 10 Studies have shown that when the combination of the prodrug 5-FC with the bacterial CD (bCD) enzyme and the production of the anticancer drug 5-FU is used in SGT, the therapeutic effect is more efficient. In this system, 5-FU, due to its small size and neutral charge, efficiently moves among adjacent cells, which leads to the formation of 5-FU-RNA and 5-FU-DNA complexes, inhibition of thymidylate synthase, and ultimately apoptosis (Figure 1).…”

“…The CD can be found in fungi and bacteria but not mammalian cells 10 . Studies have shown that when the combination of the prodrug 5‐FC with the bacterial CD (bCD) enzyme and the production of the anticancer drug 5‐FU is used in SGT, the therapeutic effect is more efficient.…”