Biomedical Engineering Reference
The success of penicillin stimulated screens for other antibacterial secondary metabolites.
This golden age of antibiotics of the 1940s and 1950s promoted research on fungal
physiology, industrial strain development and large-scale fermentation methods. In addition
to anti-infectives, many other important fungal-derived pharmaceuticals were isolated
during this systematic search for beneficial metabolites, including cholesterol-lowering
mevalonins (the “statins”) and immunosuppressant cyclosporins (Monghan and Tkacz,
1990; Von Wartburg and Trabor, 1986). Understanding of penicillin synthesis at the
molecular level was recently advanced by the sequencing of P. chrysogenum 's 32.19 Mb
genome (van den Berg et al ., 2008 ).
8.2.3 Citric acid
Citric acid is another filamentous fungal product that was key to the development of
modern industrial microbiology (Bentley and Bennett, 2008). This organic acid was
originally isolated from citrus fruit and is used as a natural preservative and flavoring to
impart a sour or acidic taste to foods and beverages. In 1893, Carl Wehmer discovered that
Penicillium species produce citric acid from sugars, but sufficient quantities could not be
produced for industrial use. American chemist James Currie at the United States
Department of Agriculture demonstrated in 1917 the abundant production of citric acid by
A. niger when cultured under the appropriate conditions (Currie, 1917). Commercial
microbial production of citric acid became a possibility in 1919 when Currie took his
fermentation method to Pfizer in Brooklyn, NY. Concomitantly, Europe began commercial
production of citric acid at Citrique Belge, now DSM, by surface fermentation of A. niger
on beet molasses.
Currie successfully pioneered the commercial production of citric acid by A. niger and
eliminated the dependence of citric acid producers on citrus fruit import from Europe during
World War I. The original Pfizer process used surface culture methods, but after the
concurrent development of deep-tank fermentation for large-scale penicillin production, the
citric acid process was adapted for large tanks and submerged culture. Techniques including
manipulating culture conditions, perfecting deep-tank fermentation, and improving product
recovery were innovated at Pfizer in the context of improving citric acid yields and laid the
foundation for modern fermentation technologies (Rodenger, 1999). Today, highly
productive A. niger strains developed through random mutagenesis generate almost all of
the entire world supply of citric acid.
Filamentous fungal fermentation is a cornerstone of bioprocess manufacturing and generates
a wide array of products used in the food, enzyme and pharmaceutical industries. Some of
the key products for these applications are reviewed here.
8.3.1 Organic acids
Fungi, especially Aspergilli , are recognized for their prolific ability to yield a repertoire of
organic acids. Conditions that produce an almost quantitative conversion of carbon substrate
into acid are exploited in the large-scale manufacture of organic acids. Moreover, many