The Industrialized Production Of ALA

5-aminolevulinic acid (ALA), a common precursor of heme, porphyrin, chlorophyll, vitamin B12 and other tetrapyrrole compounds, widely exists in microorganisms, plants and animal cells. For no toxicity to humans and animals, A1A is a pollution-free green pesticide, which can be easily degraded in the environment. As the second generation of photodynamic therapy drugs, ALA and it’s ester derivatives are more and more widly used in the treatment of skin cancer, acne, condyloma acuminatum. Therefore, ALA shows broad market prospect in the agricultural and medical fields.The purpose of this study is to accomplish industrial production of ALA with the recombinant strain E.coli Rosetta (DE3)/pET-28a-hemA.On the basis of previous studies, the different nitrogen sources and carbon sources were investigated in shake flasks. Then the results were amplified in a 15 L fermentor. With further optimization of ferment process, the ALA yield reached 9 g/L. At the same time, the cost of raw materials was reduced greatly, making the industrial production cost decrease.The separation process and the extraction technology of ALA were studied. Via ion exchange chromatography, the extraction yield of ALA reached 84%.The refining, concentration and crystallization of eluent from ion exchange process were studied. The 53.6% crystallization yield of ALA-HCl was obtained, while the purity of ALA-HC1 was 98.8% in primary crystallization. With the second crystallization, the total crystallization yield reached 80%.Chemical synthesis method of ALA-OMe-HCl was preliminary studied. The purity of obtained ALA-OMe-HCl crystal was 97.64%, while the yield of ALA-OMe-HCl from ALA·HC1 was 102.84%(W/W).Finally, with obtained process control parameters, the industrialized production of ALA on 20 t fermentor was successfully accomplished. The yield of ALA reached 6.88 g/L, while the extraction yield was 82.55%. Meanwhile, the crystallization yield of Ala-HCl was 46.55%, while the purity of ALA-HC1 reached 99%.