Trypanosoma brucei proliferates normally even after losing all S-adenosylhomocysteine hydrolase genes.

S -adenosylhomocysteine (SAH) hydrolase is the enzyme responsible for breaking down SAH into adenosine and homocysteine. It has long been believed that a deficiency of this enzyme leads to SAH accumulation, subsequently inhibiting methyltransferases responsible for nucleic acids and proteins, which severely affects cell proliferation. To investigate whether targeting this enzyme could be a viable strategy to combat Trypanosoma brucei , the causative agent of human African trypanosomiasis, we created a null mutant of the SAH hydrolase gene in T. brucei using the Cre/loxP system and conducted a phenotype analysis. Surprisingly, the null mutant, where all five SAH hydrolase gene loci were deleted, exhibited normal proliferation despite the observed SAH accumulation. These findings suggest that inhibiting SAH hydrolase may not be an effective approach to suppressing T. brucei proliferation, making the enzyme a less promising target for antitrypanosome drug development. • TbSAHH existed as a multicopy gene in T. brucei. • TbSAHH null mutant showed normal growth in culture. • Levels of S-adenosylhomocysteine and S-adenosylmethionine were elevated in TbSAHH null mutant. • TbSAHH is a less attractive target for antitrypanosome drugs. [ABSTRACT FROM AUTHOR]