Enhanced production of 5-aminolevulinic acid by repeated addition of levulinic acid and supplement of precursors in photoheterotrophic culture of Rhodobacter sphaeroides

When levulinic acid (LA) was added repeatedly in the photosynthetic culture of Rhodobacter sphaeroides to maintain its concentration at a constant (low) level, the activity of 5-aminolevulinic acid (ALA) dehydratase could be kept low enough to reduce the synthesis of porphobilinogen from ALA formed. This brought about the extracellular accumulation of ALA, while cellular growth was partially retarded. In this condition, the intermittent or continuous supplement of a fixed amount of the pre-cursors (glycine and succinate) to reduce the inhibitory effects of glycine on growth could enhance the ALA accumulation twice as much as when the same amount of the precursors was supplied all at once.