Biomedical Engineering Reference
In-Depth Information
organic acid-producing organisms tolerate low pH, thereby reducing production costs by
eliminating the need for neutralization and minimizing contamination. Several fungal-
derived acids have significant commercial value and have found wide ranging applications
in the food, feed, pharmaceutical and polymer industries. Citric, gluconic, itaconic and
lactic acids are manufactured by fungal fermentations and are of the most commercial
importance. Oxalic, fumaric and malic acids can also be made via industrial bioprocesses,
but the market demand is currently small because competing chemical conversion routes are
more economical (Magnuson and Lasure, 2004). The commercial success of fungal
fermentation is ultimately based on the rapid and economical conversion of sugar to acid
and the process of product recovery (Magnuson and Lasure, 2004). Thus, only a small
number of fungal-produced acids are manufactured on an industrial scale, despite the fact
that fungi make a diversity of organic acids.
Citric acid is an excellent example of an industrially produced fungal primary metabolite
and is a true bulk commodity. Almost the entire world supply of citric acid is made by
A. niger in submerged fermentation processes, with an estimated global production of
1.7 million tons in 2007 (Berovic and Legisa, 2007). Citric acid is the most ubiquitous
acidulant in foods, beverages and pharmaceuticals. The US Food and Drug Administration
classifies citric acid and many A. niger -derived enzymes as GRAS (Generally Recognized
as Safe), a highly desired category, because this organism has a long history of safe, non-
pathogenic and non-toxigenic use (Schuster et al ., 2002). The properties of citric acid that
form the basis for its broad range of applications include acidity and buffering capacity, taste
and flavor, and chelation of metal ions. Industrial uses of citric acid include detergent
manufacturing, electroplating and leather tanning. Citric acid is also used as a preservative
for stored blood and a buffer and antioxidant in the pharmaceutical and cosmetic industries
(Schuster et al ., 2002 ).
The manufacture of A. niger -derived citric acid conducted today is much more
efficient and economical than the original Pfizer method. The majority of citric acid is
currently generated by submerged fermentation methods, though the more labor
intensive, original method of surface fermentation is still in use (Sahasrabudhe and
Sankpal, 2001). Modern fermentation technologies can yield 95 kg citric acid per 100 kg
of supplied sugar with the best producer strains and optimized production conditions
(Karaffa and Kubicek, 2003). High yields of citric acid accumulation require a unique
combination of several unusual nutrient conditions, including 15-20% w/v readily
metabolized sugars, suboptimal amounts of phosphate and nitrogen to limit fungal
growth and low levels of heavy metal ions including manganese. Maintaining a distinct
fungal morphology in submerged culture is a good indicator of high levels of citric acid
outflow (Karaffa and Kubicek, 2003). Germinating spores form short, stubby, forked,
bulbous hyphae that aggregate into smooth, round pellets (Figure 8.1). Individual pellets
are 200-500 microns in diameter. This tight-pelleted morphology is dependent on
appropriate nutrient composition, especially maintaining low manganese levels (Kisser
et al ., 1980 ).
Fungal fermentation also produces gluconic and itaconic acids, which are of lesser
economic importance than citric acid. Gluconic acid, produced by A. niger , is used
primarily as a food additive as well as for cleaning and finishing of metal surfaces and
some pharmaceutical applications (Ramachandran et al ., 2006 ). The estimated annual
global production of gluconic acid is 60 000 tons. Itaconic acid is produced by A. terreus
in submerged fermentation processes similar to that for citric acid accumulation (Willke
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