In E. coli, the biosynthesis begins with phosphorylation of 5-phosphoribosyl-pyrophosphate (PRPP), catalyzed by ATP-phosphoribosyl transferase. Phosphoribosyl-ATP converts to phosphoribosyl-AMP (PRAMP). His4 then catalyzes the formation of phosphoribosylformiminoAICAR-phosphate, which is then converted to phosphoribulosylformimino-AICAR-P by the His6 gene product. His7 splits phosphoribulosylformimino-AICAR-P to form -erythro-imidazole-glycerol-phosphate. After, His3 forms imidazole acetol-phosphate releasing water. His5 then makes -histidinol-phosphate, which is then hydrolyzed by His2 making histidinol. His4 catalyzes the oxidation of -histidinol to form -histidinal, an amino aldehyde. In the last step, -histidinal is converted to -histidine.
In general, the histidine biosynthesis is very similar in plants and microorganisms.
HisG → HisE/HisI → HisA → HisH → HisF → HisB → HisC → HisB → HisD  (HisE/I and HisB are both bifunctional enzymes)
The enzymes are coded for on the His operon. This operon has a distinct block of the leader sequence, called block 1:
Met-Thr-Arg-Val-Gln-Phe-Lys-His-His-His-His-His-His-His-Pro-Asp
This leader sequence is important for the regulation of histidine in E. coli. The His operon operates under a system of coordinated regulation where all the gene products will be repressed or depressed equally. The main factor in the repression or derepression of histidine synthesis is the concentration of histidine charged tRNAs. The regulation of histidine is actually quite simple considering the complexity of its biosynthesis pathway and, it closely resembles regulation of tryptophan. In this system the full leader sequence has 4 blocks of complementary strands that can form hairpin loops structures. Block one, shown above, is the key to regulation. When histidine charged tRNA levels are low in the cell the ribosome will stall at the string of His residues in block 1. This stalling of the ribosome will allow complementary strands 2 and 3 to form a hairpin loop. The loop formed by strands 2 and 3 forms an anti-terminator and translation of the his genes will continue and histidine will be produced. However, when histidine charged tRNA levels are high the ribosome will not stall at block 1, this will not allow strands 2 and 3 to form a hairpin. Instead strands 3 and 4 will form a hairpin loop further downstream of the ribosome. The hairpin loop formed by strands 3 and 4 is a terminating loop, when the ribosome comes into contact with the loop, it will be “knocked off” the transcript. When the ribosome is removed the His genes will not be translated and histidine will not be produced by the cell.