Production Strains for Metabolites with Unusual Biochemistry

Production Strains for Metabolites with Unusual Biochemistry 

Conventional metabolic pathway engineering concepts and tools were appropriate to develop B. suhtilis Marburg 168 into efficient production strains for the vitamins riboflavin and pantothenic acid. For both compounds, the biochemical reactions from common metabolites to the final products were known to a great detail. Pantothenic acid biosynthesis involves efficient enzymes with high turnover numbers that catalyze standard biochemical reactions. The enzymes of the riboflavin pathway catalyzing more complex reactions are relatively slow, but strains overexpressing these enzymes could be furnished with sufficient biocat-alytic activity. 

The biosynthesis pathways of the vitamins thiamine (Bl), pyridoxine (B6), and biotin (B7) have been elucidated during the last 10 years to some detail. It became clear that in all cases enzymes catalyzing unusual or complex biochemical reaction mechanisms are involved, which perform at least in vitro with very low catalytic efficiency. Previous attempts to breed B. suhtilis production strains for these vitamins as a base for the development of superior processes to supersede the decades old chemical processes are reviewed here briefly. These efforts followed the blueprints that were successful for other metabolites like amino acids, nucleotides, the vitamins mentioned above, and others. However, the metabolic fluxes toward the vitamins Bl, B6, and B7 have proven to be particularly adamant to engineering. The strains that were obtained overproduced these value compounds only at marginal levels. 

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Production Strains for Metabolites with Unusual Biochemistry 271... 

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