5-Aminolevulinic Acid: Production by Fermentation, and Agricultural and Biomedical Applications

5-Alninolevulinic acid (ALA) is kno\vn as a C0l11ffiOIl precursor of tetrapyrrole C0111pounds (e.g. chlorophyll, henle and vitamin Bl~) in all living organisJns (Figure 7. I). ALA has the potential to be widely used as a biodegradable herbicide (Rebeiz et al., 1984), insecticide (Rebeiz et ai., 1988), and in photodynanlic cancer therapy (Kennedy el al., 1990). Recently, Hotta et al. (1997) have reported that a low level of ALA stitnulates plant growth and increases the yields of several crops. ALA also has potential for LIse as an active substrate for the chemical synthesis of nlaterials. For these reasons, a nunlber of ALA production nlethods have been developed. ALA has been synthesized chenlically via selective reduction of acyl cyanides (Pfaltz and An\var~ 1984) or via dye-sensitized oxygenation ofN-furfurylphthalilnide (Takeya et al., 1989) (Figure 7.2). However, the chenlical synthesis of ALA requires at least four reaction steps and the yield is less than 60%. The high cost ofproductlon of ALA has thus far limited its cOlunlcrcia) utilization. Microorganisills such as Clostridhl111 thernlO{lCeticul1l (Koesnandar et al., 1989), methanogens (Lin et al., 1989), Chlorella spp. (Sasaki et al., 1995: Ano et al., 1999, 20(0). and photosynthetic bacteria (van der Mariet and Zeikus., ]996; Sasaki et al., 1989, 1990, 1993., 1995; Tanaka el al., 1991, 1994a,b) produce ALA in considerable anlounts. The ALA production by photosynthetic bacteria, ho\vever, requires light illll1nination and has been found to be sensitive to aeration. A crude extract froln