The collaborative efforts of the synthetic biology and microbial metabolic engineering teams at the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, have led to a groundbreaking achievement in the field of synthetic biology. Through a sophisticated system engineering approach, they have successfully engineered Escherichia coli to develop an efficient de novo synthesis pathway for nicotinamide mononucleotide (NMN, CAS No. 1094-61-7), significantly boosting its metabolic production within the organism.
In this innovative journey, researchers first employed advanced gene editing techniques to precisely knock out the pncC and nadR genes, resulting in a quantum leap in NMN production compared to the original strain, with an increase of over 100 times. Building on this success, they further refined the de novo synthesis pathway for NMN and seamlessly integrated it with the NadV-mediated biosynthetic pathway. Additionally, the introduction of two efficient transporter proteins greatly facilitated the absorption of nicotinamide (NAM) and the efflux of NMN, pushing the production of NMN to a new height of approximately 1300 micromolar.
Their pursuit of excellence did not stop there. By optimizing the PRPP (5-phosphoribosyl-1-pyrophosphate) synthetase, researchers injected a powerful impetus into the production of NMN, ultimately achieving a stunning yield of over 3000 micromolar after just 24 hours of fermentation in shake flasks.
This research not only offers fresh insights into the NAD+ salvage pathway and its pivotal role in the energy metabolism of Escherichia coli but also opens up broader application prospects for synthetic biology in the biopharmaceutical and health industries, infusing robust innovation into the thriving development of this field.