Industrial Biotransformations

Nicotinic acid hydroxylase
Achromobacter xylosoxidans
Fig. 1.5.1.13 – 2
● The process takes place in two phases (see flow scheme):
Phase 1: Growth of cells in a fermenter (chemostat) on niacin and subsequent storage of biomass
in cooled tanks.
Phase 2: Addition of biomass to niacin solution, incubation, separation of biomass and purification
of product.
● The product is precipitated by the addition of acid.
EC 1.5.1.13
● Alternatively, the integration of the two phases into an one reaction vessel fed-batch operation
is possible (product concentration of 75 g · L –1 in 25 h). This procedure is not used on an
industrial scale.
● Also, a continuous process was developed as a ‘pseudocrystal fermentation’ process. The substrate
is added in its solid form and the product crystallizes out of the reaction solution. The
process takes advantage of the fact that the Mg-salt of niacin is 100 times more soluble in H 2O
at neutral pH than Mg-6-hydroxynicotinate. The pH is titrated to 7.0 with nicotinic acid. The
concentration of Mg-nicotinate is regulated to 3 % using conductivity measurement techniques
and direct addition of the salt. Mg-6-hydroxynicotinate is collected in a settler.
● Niacin hydroxylase works only in the presence of electron-transmitting systems such as cytochrome,
flavine or NADP + , and therefore air needs to be supplied to facilitate the cofactor
regeneration. The oxygen-transfer rate limits the reaction.
● In contrast to the biotransformation the chemical synthesis of 6-substituted nicotinic acids is
difficult and expensive due to difficulties in the separation of by-products.
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