Production of N-acetylneuraminic acid in Escherichia coli using different carbon sources
N-acetylneuramic acid,the most common type of sialic acids,generally locates at the terminal of glycoprotein and glyco-lipid on the surface of cell membrane,where it performs a variety of biological functions.Because of its unique physiological and biochemi-cal properties,it is more and more widely used in pharmaceutical,cosmetic and food industries,and its demand will continue to increase.The heterologous biosynthesis of N-acetylneuraminic acid in Escherichia coli needs to compete precursors with the process of central carbon metabolism.Therefore,the efficiency of carbon source utilization and the distribution of carbon metabolic flux in cell growth and N-acetyl-neuraminic acid synthesis directly affect the synthesis efficiency of N-acetylneuraminic acid.In this study,the effects of glucose,glycerol and their mixture on the synthesis of N-acetylneuraminic acid were compared from the point of view of carbon source utilization regulation.When using single glucose carbon source,the knockout of pfkA in strain NEU5AC-2 weakened the intensity of central carbon metabolism,reduced the accumulation of by-product acetic acid,and coordinated the supply of precursors GlcNAc and PEP.NEU5AC-2 produced 23.8 g/L N-acetylneuraminic acid after 38 h of fed-batch fermentation in a 5-L bioreactor,which obtained higher level of fermentation production and strong industrial application potential.This study shed light on similar studies using metabolites in EMP as precursors for the biosynthesis of heterologous chemicals.
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