Biosynthesis of UDP-ManNAcA in the Methanococcales. The isomerizing glutamine-Fru-6-P transaminase (GlmS; EC 2.6.1.16; MJ1420 or MMP1680) catalyzes the isomerization of Fru-6-P and its transamination from the l-glutamine amide, producing GlcN-6-P. Phosphoglucosamine mutase (GlmM; EC 5.4.2.10; MJ1100 or MMP1077) catalyzes the transfer of phosphate from GlcN-6-P to the anomeric position, forming α-d-glucosamine-1-phosphate (GlcN-1-P). The bifunctional GlcN-1-P uridylyltransferase/acetyltransferase (GlmU; EC 2.7.7.23/2.3.1.57; MJ1101 or MMP1076) catalyzes the acetylation of the 2-amino group using acetyl-CoA and the transfer of GlcNAc-1-P to UTP, releasing pyrophosphate and UDP-GlcNAc. The UDP-GlcNAc 2-epimerase (WecB; EC 5.1.3.14; MJ1504 or MMP0705) catalyzes the isomerization of UDP-GlcNAc to produce UDP-ManNAc. Finally, the UDP-ManNAc 6-dehydrogenase (WecC; EC 1.1.1.-; MJ0468 or MMP0706) catalyzes the four-electron oxidation of UDP-ManNAc, reducing NAD+ and releasing UDP-ManNAcA.