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Background  4-Hydroxymandelic acid (4-HMA) is a valuable aromatic fine chemical and widely used for production of pharmaceuticals and food additives. 4-HMA is conventionally synthesized by chemical condensation of glyoxylic acid with excessive phenol, and the process is environmentally unfriendly. Microbial cell factory would be an attractive approach for 4-HMA production from renewable and sustainable resources.    Results  In this study, a biosynthetic pathway for 4-HMA production was constructed by heterologously expressing the fully synthetic 4-hydroxymandelic acid synthase ( shmaS)  in our  l -tyrosine-overproducing  Escherichia coli  BKT5. The expression level of  shmaS  was optimized to improve 4-HMA production by fine tuning of four promoters of different strength combined with three plasmids of different copy number. Furthermore, two genes  aspC  and  tyrB  in the competitive pathway were deleted to block the formation of byproduct to enhance 4-HMA biosynthesis. The final engineered  E. coli  strain HMA15 utilized glucose and xylose simultaneously and produced 15.8 g/L of 4-HMA by fed-batch fermentation in 60 h.    Conclusions  Metabolically engineered  E. coli  strain for 4-HMA production was designed and constructed, and efficiently co-fermented glucose and xylose, the major components in the hydrolysate mixture of agricultural biomass. Our research provided a promising biomanufacturing route to produce 4-HMA from lignocellulosic biomass.    Electronic supplementary material  The online version of this article (doi:10.1186/s12934-016-0489-4) contains supplementary material, which is available to authorized users.

Engineering Escherichia coli for production of 4-hydroxymandelic acid using glucose–xylose mixture