Dihydroorotate dehydrogenase (DHODH), in the de novo pyrimidine biosynthetic 
pathway, is the fourth enzyme of pyrimidine synthesis and is used to oxidize 
dihydroorotate and hence to orotat. We cloned and characterized here the dhod of 
silkworms, Bombyx mori. The full-length cDNA sequence of dhod is 1339 bp, 
including an open reading frame (ORF) of 1173 bp that encoded a 390 amino acid 
protein. And two domains were involved in the Dihydroorotate dehydrogenase amino 
acid sequence of silkworms, Bombyx mori (BmDHODH), namely a DHO_dh domain and a 
transmembrane domain in N-termina. The silkworm dhod is expressed throughout 
development and in nine tissues. Moreover, knockdown of the silkworm dhod gene 
reduced cell growth and proliferation through G2/M phase cell cycle arrest. 
Similarly, DHODH inhibitor (leflunomide) also reduced cell growth and 
proliferation, with a significant decrease of cyclin B and cdk2. DHODH is the 
fourth enzyme of pyrimidine synthesis, so we also found that leflunomide can 
inhibit, at least in part, the endomitotic DNA replication in silk glands cells. 
These findings demonstrate that downregulation of BmDHODH inhibits cell growth 
and proliferation in silkworm cells, and the endomitotic DNA replication in silk 
gland cells.