代谢工程在核黄素生产上的应用

Application of Metabolic Engineering in Riboflavin Production

核黄素(维生素B2)为天然水溶性的B族维生素,是维持机体代谢所必须的营养物质。目前核黄素的工业化生产主要有微生物发酵法和化学半合成法两种,其中微生物发酵法以生产工艺简单、原料廉价、环境友好以及资源可再生等优点而倍受世界核黄素生产商的青睐。代谢工程是近二十年来发展起来的新型学科,主要利用分子生物学技术对细胞进行遗传修饰,从而改进产物生成或细胞特性。为进一步提高核黄素产量,通过代谢工程手段构建出了核黄素高产菌株,其中尤以枯草芽孢杆菌最为成功。要得到较高的核黄素产率,必须保证碳架、能量等价物以及氧化还原辅(酶)因子在细胞代谢过程中处于适当的比率。以枯草芽孢杆菌进行核黄素生产为例,主要从增强碳源和能源利用效率、增强核黄素生物合成途径代谢流以及解除核黄素生物合成过程中的反馈调节方面综述了代谢工程在指导核黄素生产方面的应用,并讨论了其未来的发展方向。

Riboflavin （ Vitamin B2） is a precursor to coenzymes such as flavin adenine dinucleotide （FAD） and flavin mononucleotide （FMN）. It can be commercially produced either by a semi-chemical synthesis or by fermentation with some microorganisms. Because of the advantages of biotechnical process, such as cost effectiveness, reduction in waste and energy and use of renewable resources, biotechnical route has become popular for riboflavin producer. In order to acquire riboflavin over-producing strains, research has been concentrated on metabolically modified strains by finalizing the relationships of genes and enzymes, dissecting the complex regulatory apparatus that governs expression of the rib genes and identifying transport gene. The engineered riboflavin overproducing Bacillus subtilis is one of the most successful examples. Metabolic engineering is a new developing subject in recent twenty years, which made celluar genetic modification to improve production or celluar peculiarity. To maximize the conversion of substrate carbon to desired end products, building blocks, energy equivalents, and redox cofactors must be guaranteed at an appropriate rate and stoichiometry by cellular catabolism. The applications and the trends of metabolic engineering in riboflavin production by Bacillus subtilis were summarized. The applications involved the improvement of the efficiency of carbon and energy utilization, enhancement of metabolic flux and deregulating of the process in riboflavin biosynthetic pathway.