Fungal Cell Factories - Food and Industrial Bioproducts and Bioprocessing - page 202

alcohol to extract diastase, now known as amylase. While working in Peoria, IL, he
originally marketed his diastase to the beer and whiskey trade as a more enzymatically-
active alternative to malting enzymes. Takamine's efforts in this endeavor were thwarted
due to personal ill health as well as labor unrest and intimations of arson. However, he
ultimately achieved business success for his commercialized enzyme “Taka-diastase”
which was marketed as a dyspepsia panacea by Parke, Davis and Company of Detroit, MI.
He was granted a US patent in 1894 for his method of producing koji diastatic enzymes;
this is thought to be the first patent for a microbial enzyme (Bennett, 1988, 2001; Machida
et al ., 2008 ).
A variety of fungal enzymes, including cellulases, amyloglucosidases, lipases and
proteases, are now commercially available, and their applications extend well beyond the
traditional use in food fermentation processes. Aspergilli , including A. niger and A. oryzae ,
enjoy an extended history of safe use and play a key role in the industrial manufacture of
many of these enzymes (Baker and Bennett, 2008). Some of Takamine's methods for
culturing filamentous fungi are still used in today's enzyme industry. Solid-state
fermentation produces higher yields of certain hydrolytic fungal enzymes than liquid
fermentation, and this process is utilized for the commercial production of glucoamylase
(GlaB) and aspartic protease (PepA) of A. oryzae and an acid-stable

α -amylase of A.

kawachii (Abe and Gomi, 2008 ).

8.2.2 Penicillin
The discovery of the fungal metabolite penicillin and its subsequent development into a
“wonder drug” was central to the innovation of modern fungal biotechnology (Wainwright,
1990; Bentley and Bennett, 2008). Bacteriologist Alexander Fleming isolated penicillin
from Penicillium notatum while at St. Mary's Hospital, London, in 1928. Fleming noted his
discovery might have therapeutic value if it could be produced in sufficient quantity
(Fleming, 1929 ).
The industrial microbial production of penicillin became a reality after the technological
breakthrough of submerged (also referred to as “deep”) fermentation methods at United
States Department of Agriculture's Northern Regional Research Laboratories (NRRL) in
Peoria, IL. With the world at war in 1941, Oxford researchers led by Drs Florey, Ernst Boris
Chain and Norman Heatley collaborated with NRRL to produce the quantities of penicillin
needed for clinical trials. In 1945 Fleming, Florey and Chain were awarded the Nobel Prize
in Medicine or Physiology “ for the discovery of penicillin and its curative effect in various
infectious diseases .”
Orville May, Percy Wells and Andrew Moyer of the NRRL Fermentation Division had
previously patented a novel submerged fermentation process in 1935, and these methods
were applied to penicillin production. Submerged culture conditions in large, aerated
vessels generated greater penicillin yields than the previous surface growth fermentation.
In addition to the development of submerged fermentation methods, penicillin yield was
greatly improved by substituting corn steep liquor in the growth medium and utilizing
higher yielding penicillin strains. After a worldwide search for higher yielding isolates,
P. chrysogenum (NRRL, 1951) cultured from a moldy cantaloupe found in a Peoria
market generated the greatest penicillin yield when grown in the submerged culture
conditions.