36 RAPER 



less subject to serious contamination. The gluconic acid fermentation is im- 

 portant because it provides a rapid and economic process for producing this 

 acid ; it is probably of even greater importance because it represented the first 

 mold fermentation conducted on a large scale where the fungus was grown 

 not as a felt on the surface of thin layers of substrate but as a submerged 

 mycelium in large tanks with rapid agitation and strong aeration. Today, 

 gluconic acid is produced in an amount estimated at about 10 million pounds 

 per annum. Some of this, in the form of its various salts, is used for the 

 preparation of pharmaceuticals used in the treatment of calcium and other 

 mineral deficiencies in man, and a considerable amount as calcium gluconate 

 is used for treatment of milk fever in cattle. The free acid is used in a 

 variety of industrial operations, and very recently in the form of its sodium 

 salt it has found an important application as a sequestering agent for the 

 removal of calcium and other metallic ions in the washing of glassware, in- 

 cluding milk bottles and other containers of this type. 



Fumaric acid is also produced by a fermentation process. The molds em- 

 ployed in this case are selected strains of Rhizopus oryzae and R. nigricans, 

 belonging to the Mucorales. Interestingly enough, the first report of the 

 mycological production of fumaric acid was by Wehmer, in 1918, who utilized 

 a special strain of A. niger, reported as A. jumaricus. Exhaustive studies by 

 Foster and Ward have shown conclusively that the aforementioned phycomy- 

 cetous fungi carry out this fermentation most effectively. Fumaric acid is pro- 

 duced in fairly large amounts and finds its greatest applications as a mordant 

 in the dyeing of textiles and in the plastics industry, but in the latter field it 

 must now compete with maleic anhydride, which is produced from benzene 

 by synthetic processes. By altering the conditions of culture and by the selec- 

 tion of other strains of R. oryzae, D-lactic acid can be produced with rea- 

 sonable efficiency. However, the mold product in this case must compete 

 with cheaper lactic acid resulting from bacterial fermentations which can 

 be operated more rapidly and with less attention to problems of contami- 

 nation; hence the mold is little used. Lactic acid production amounts to 

 several million pounds per year, of which almost half is of edible grade and 

 is used primarily in foods and in food processing. The remaining product, 

 representing technical grade, finds a variety of industrial applications. 



Itaconic acid represents yet another product of mold fermentation which 

 can be produced in good yield. The earliest report of its production (1931) 

 was by a Japanese investigator, Kinoshita, who identified it as a metabolic 

 product of A. itaconicus, a mold possessing osmophilic growth requirements 

 which precluded its economic exploitation. Subsequent studies by Professor 

 Harold Rastrick and his associates (1939) in London revealed that this acid 

 was produced in varying amounts by strains of the common soil mold, A. 

 terreus. Starting from this point, Lockwood, Moyer, and other investigators 

 at the Northern Regional Laboratory developed during the 1940's a process 



