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Vitamins are essential organic small molecules that maintain normal physiological functions in living organisms. Most vitamins cannot be synthesized autonomously by the human body and must be supplemented through food or pharmaceuticals to meet physiological demands. Driven by the growing emphasis on healthy diets and the advancement of carbon neutrality strategies, the development of bio-manufacturing technologies for vitamins has become increasingly significant. While China is a global leader in vitamin production, technical bottlenecks persist in the areas of high-end vitamins and critical intermediates. Taking the representative water-soluble vitamin B5 (VB5) as an example, the current state of vitamin synthesis technologies were systematically summarized. The evolution of VB5 manufacturing technologies, from first-generation chemical synthesis, second-generation chemo-enzymatic/enzymatic catalysis, to third-generation fully biofermentation-based synthesis were elaborated, highlighting the iterative advancements in vitamin synthesis pathways. The applications of multi-strategy approaches in third-generation fully biofermentation-based synthesis for VB5 production were examined, including the enhancement of sugar uptake systems, redirection of central carbon metabolism flux, cofactor balancing, regulation of competitive pathways, and optimization of transport systems. Additionally, interdisciplinary research directions such as systematic metabolic engineering modification coupled with fermentation process optimization were proposed. These strategies aimed to drive continuous innovation in vitamin bio-manufacturing technologies, providing robust support for the high-quality development and enhancing international competitiveness of China's vitamin industry.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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