Integration of random mutagenesis and adaptive laboratory evolution for improving pyrroloquinoline quinone production in Hyphomicrobium denitrificans

We first used oxidative stress as selecting pressure to increase the production of PQQ in Hyphomicrobium denitrificans H4-45 by combining UV-LiCl mutagenesis and ALE. second, We further increased PQQ production by optimizing batch and fed-batch fermentation processes in a 3.7 L bioreactor. Finally, the whole genome resequencing analysis of the evolved strain and parental strain was performed to assess what mechanisms might be responsible for the increased PQQ production.