Combing with redox regulation via quorum-sensing system and fermentation strategies for improving D-pantothenic acid production

Microbial production of D-pantothenic acid (D-PA) has become an important research area, as D-PA is an essential vitamin widely applied in food, feed, chemical and pharmaceutical industries. Here both dynamic regulations of redox metabolism and fermentation strategies were applied to enhancing D-PA biosynthesis in Escherichia coli W3110. Firstly, a quorum-sensing (QS) system for redox regulation developed, in which zwf and nadK overexpression were shown to be effective for enhancing D-PA production. Based on this, a strain DPA11/p LBCWK was constructed with D-PA titer at 4.19 g/L in flask. Moreover, the fermentation strategies including pH-feedback feeding and gradient β-alanine feeding were introduced, under optimal conditions, the strain DPA11/p LBCWK could produce 48.21 g/L D-PA in 5 L fermenter, with the specific productivity of 0.72 g/L·h and the yield of 0.33 g/g glucose. These modification strategies were proved effective and would provide valuable reference for biosynthesis of other chemicals. • The redox regulation improved the yield of D-pantothenic acid. • A quorum-sensing system was used for D-pantothenic acid synthesis for the first time. • A 48.21 g/L D-pantothenic acid was obtained in feeding fermentation.