Methanol-based cadaverine production by genetically engineered Bacillus methanolicus strains

Methanol is regarded as an attractive substrate for biotechnological production of value-added bulk products, such as amino acids and polyamines. In the present study, the methylotrophic and thermophilic bacterium Bacillus methanolicus was engineered into a microbial cell factory for the production of the platform chemical 1,5-diaminopentane (cadaverine) from methanol. This was achieved by the heterologous expression of the Escherichia coli genes cadA and ldcC encoding two different lysine decarboxylase enzymes, and by increasing the overall L-lysine production levels in this host. Both CadA and LdcC were functional in B.methanolicus cultivated at 50 degrees C and expression of cadA resulted in cadaverine production levels up to 500mgl(-1) during shake flask conditions. A volume-corrected concentration of 11.3gl(-1) of cadaverine was obtained by high-cell density fed-batch methanol fermentation. Our results demonstrated that efficient conversion of L-lysine into cadaverine presumably has severe effects on feedback regulation of the L-lysine biosynthetic pathway in B.methanolicus. By also investigating the cadaverine tolerance level, B.methanolicus proved to be an exciting alternative host and comparable to the well-known bacterial hosts E.coli and Corynebacterium glutamicum. This study represents the first demonstration of microbial production of cadaverine from methanol.