Biomedical Engineering Reference
In-Depth Information
folding, lower expression and reduced activity. More basic knowledge on
the production machinery is needed also to allow for large scale cost effi cient
production of thermostable enzymes.
Currently, the biggest players in the production of commercial cellulases
are the enzyme manufacturers Danisco/Genencor and Novozymes. Various
products derived from
T. reesei
and
A. niger
are available as cocktails either
for cellulose and/or hemicellulose degradation. Depending on the type
of substrate needed to be converted and the pretreatment method, these
enzyme cocktails can be added alone or in different combinations (see for
example Banerjee et al. 2010). The latest enzyme product from Novozymes,
introduced in 2010, Cellic CTec2 claims an enzyme cost up to $0.5/gallon
ethanol. Even though the enzyme cost contribution to the ethanol price is
still high, the price gap between bioethanol production from starch and
lignocellulosic biomass is closing up fast.
FUNGAL ENZYMES IN PHARMACEUTICAL APPLICATIONS
For well over a century fungal enzymes are indirectly used in the
production of pharmaceuticals as they convert the available feed stocks
for fungi into useful secondary metabolites as penicillins which are
harvested for human applications. Alternatively, fungal enzymes can
act as biocatalysts converting a chemically synthesized substrate as for
example cis-aropenylphosphonic acid directly into the broad-spectrum
antibiotic fosfomycin. More recently, fungal enzymes themselves have
been developed as a pharmaceutical product.
Fungal Enzymes in Natural Product Biosynthesis
Fungi live in very diverse environments, which led to the evolution
of a versatile range of secondary metabolites in order to fi ght their
competitors or to co-inhabit ecological communities (reviewed by O'Brien
and Wright 2011). With ever-increasing resistance of pathogens towards
commonly used antibiotics (like the archetype penicillin), fungi are a
rich source of new antibiotics with subsequent good production systems.
The classical drug discovery approach has identifi ed many interesting
fungal compounds, but most of them do not enter the clinic for several
reasons. High production cost being one of the main reasons, besides
effi cacy and unwanted side-effects. For example taxol, an existing natural
pharmaceutical compound with proven effi cacy, has been reported to be
produced by many different fungi but that has not yet lead to a profi table
microbial synthesis process (Flores-Bustamante et al. 2010) as for other
compounds (Zhao et al. 2011).
