Enzymatic regeneration and conservation of ATP: challenges and opportunities

Adenosine triphosphate (ATP), the universal energy currency of life, has a central role in numerous biochemical reactions with potential for the synthesis of numerous high-value products. ATP can be regenerated by three types of mechanisms: substrate level phosphorylation, oxidative phosphorylation, and photophosphorylation. Current ATP regeneration methods are mainly based on substrate level phosphorylation catalyzed by one enzyme, several cascade enzymes, orin vitrosynthetic enzymatic pathways. Among them, polyphosphate kinases and acetate kinase, along with their respective phosphate donors, are the most popular approaches forin vitroATP regeneration. Forin vitroartificial pathways, either ATP-free or ATP-balancing strategies can be implementedviasmart pathway design by choosing ATP-independent enzymes. Also, we discuss some remaining challenges and suggest perspectives, especially for industrial biomanufacturing. Development of ATP regeneration systems featuring low cost, high volumetric productivity, long lifetime, flexible compatibility, and great robustness could be one of the bottom-up strategies for cascade biocatalysis andin vitrosynthetic biology.

Automated summary

Adenosine triphosphate (ATP) serves as the universal energy currency of life, playing a central role in biochemistry. ATP can be regenerated through various mechanisms, with polyphosphate kinases and acetate kinase being popular approaches. Development of cost-effective, high productivity ATP regeneration systems is crucial for industrial biomanufacturing in the field of synthetic biology.