Microbiological Production and Herbicidal Mechanism of $\delta$-Aminolevulinic Acid as a Tetrapyrrole-Dependent Photodynamic Herbicide

-Aminolevulinic acid(ALA) has been well known as an intermediate for the biosynthesis of tetrapyrroles such as chlorophyll, heme, bacteriochlorophyll, and vitamin B12 analogues in human, plants, animals, and microorganisms. Recently, ALA has received great attention as a new biodegradable pesticide that is inhibitory to weeds but not harmful to crops, animals, and human, and as a prodrug for photodynamic diagnosis and therapy of cancer. In addition, ALA has been reported to promote the growth and yield of rice, corn, kidney bean, potato, garlic and Vigna species at low concentrations, and to improve salt tolerance of cotton seedlings. ALA is synthesized intracellularly from glycine and succinate by ALA synthase(ALAS) in human, animals and microorganisms, not plants. However, ALA dehydratase(ALAD) catalyzes the condensation of two molecules of ALA into porphobilinogen. To enhance the accumulation of ALA in the biological production, levulinic acid as a competitive inhibitor of ALAD in tetrapyrrole biosynthetic pathway should be added to the culture medium. ALA is very expensive because it is usually synthesized chemically via complex processes. Therefore, biological production using microorganisms has been suggested as an inexpensive way to produce ALA. It has been well known that photosynthetic Rhodospirillaceae such as mainly Rhodospirillum, Rhodobacter, and Rhodopseudomonas species can extracellularly excrete ALA. Most recently, ALA was produced from the transgenic E. coli that overexpressed ALAS by inserting a hemA gene from other microorganism. ALA was named as a tetrapyrrole-dependent photodynamic herbicides that force green plants to accumulate undesirable amount of metabolic intermediates of the chlorophyll and heme metabolic pathway in darkness. In the light, the accumulated tetrapyrroles induce the formation of singlet oxygen that kills the treated plants by oxidation of their cellular membranes as in the action of diphenyl ether herbicides. Development of ALA as a new herbicide involves the joint utilization with activators of the chlorophyll biosynthetic pathway, such as 2,2-dipyridyl. During the subsequent light period the accumulated tetrapyrroles act as potent photodynamic sensitizers, which in turn results in the death of susceptible plants