5-aminolevulinic acid (ALA) has extensive use in photodynamic cancer therapy, tumor diagnosis, and agriculture. In the microbial production of ALA, most efforts have focused on engineering enzymes and the metabolic pathways involved in ALA biosynthesis. The aim of this study was to enhance ALA production using recombinant Streptomyces coelicolor expressing the ALA synthase gene (hem A) of Rhodobacter sphaeroides with a novel two-stage pH control strategy. Batch cultures were performed in production medium at different pH values. Although cells grew well at neutral pH (6.8–7.2), the highest amount of ALA was produced with a long culture time (140 h) at a weakly acidic pH (5.5–6.0). In response, a two-stage pH control strategy was developed in which pH was maintained at 6.8–7.2 for cell growth and then shifted to 5.5–6.0 to promote ALA synthesis, resulting in a significant enhancement in ALA production compared to a one-stage pH control strategy. The titer of ALA was further improved up to 482 mg/L in the two-stage pH culture by supplying more glucose in the medium and shifting the pH during the early phase of cultivation.

5-氨基乙酰丙酸 (ALA) 在光动力癌症治疗、肿瘤诊断和农业中具有广泛的用途。在 ALA 的微生物生产中，大多数努力都集中在工程酶和 ALA 生物合成中涉及的代谢途径上。本研究的目的是使用表达球状红杆菌 ALA 合酶基因 (hem A) 的重组天蓝色链霉菌来提高 ALA 产量。采用新颖的两阶段 pH 控制策略。在不同pH值的生产培养基中进行分批培养。尽管细胞在中性 pH 值（6.8-7.2）下生长良好，但在弱酸性 pH 值（5.5-6.0）下长时间培养（140 小时）会产生最高量的 ALA。作为回应，开发了一种两阶段 pH 控制策略，其中 pH 维持在 6.8-7.2 以促进细胞生长，然后转变为 5.5-6.0 以促进 ALA 合成，与单阶段相比，ALA 产量显着提高。 pH控制策略。通过在培养基中提供更多的葡萄糖并在培养的早期阶段改变 pH 值，ALA 的滴度在两阶段 pH 值培养中进一步提高至 482 mg/L。