38 RAPER 



gated led to the development of a process for the production of this needed 

 vitamin in substantial yield. Today, riboflavin is produced in large amounts 

 by the fermentation industry. It is manufactured by the use of either Ashbya 

 or Eremothecium, which became available after the war. Concurrent with 

 these developments a process was worked out for the production of riboflavin 

 by purely chemical synthesis. However, the microorganisms can effect its 

 production with such efficiency and economy that the bulk of the current 

 production stems from the microbiological process. For many purposes the 

 latter method of manufacture possesses a distinct advantage, for if the vita- 

 min is to be used in animal feeds, it can be recovered as a crude concen- 

 trate which is used in proportion to its vitamin content. The annual pro- 

 duction of riboflavin today amounts to nearly 300,000 pounds (expressed as 

 pure riboflavin) with a current sales price in the neighborhood of $40.00 

 per pound for U.S.P. grade, whereas that of feed grade is about $30.00 per 

 pound of riboflavin contained in approximately 115 pounds of vitamin-rich 

 supplement. Riboflavin is also produced by species of the genus Clostridium, 

 anaerobic bacteria used for the microbial production of acetone and butyl 

 alcohol. In this case the vitamin-rich fermentation residue is dried and sold 

 as a feed supplement. 



The microbiological production of cyanocobalamin, or vitamin B12, is 

 equally important, and processes for its manufacture arose from a singu- 

 larly interesting sequence of events. For many years it had been known 

 that pernicious anemia could be held in check by the administration of liver 

 extracts. In 1947, Shorb found that the effectiveness of these extracts in 

 controlling this disease could be correlated with their ability to support the 

 growth of certain fastidious bacteria belonging to the genus Lactobacillus. 

 The following year research investigators at Merck and Company discovered 

 that the extracts contained a highly active principle, which in a pure state 

 represented a red crystalline compound. This substance was nutritionally 

 essential for the Lactobacilli, and significantly, the amount of their growth 

 was proportional to its content in the liver extracts. Soon thereafter they 

 demonstrated that the compound showed positive hematological activity when 

 administered to patients suffering from Addisonian pernicious anemia. Iden- 

 tity with the anti-anemia factor in liver was established, and it was reported 

 as vitamin B12. Later it was found that this vitamin could be extracted also 

 from the residues of the streptomycin fermentation, and subsequently, that 

 it could be obtained in even greater yield from the residues of the Aureo- 

 mycin fermentation. In fact, it was disclosed that many of the Actinomycetes 

 produced this substance, and it was logically suspected that a determined 

 search might reveal a species or strain which would produce it in even 

 greater amount. Harlow H. Hall of the Northern Regional Laboratory con- 

 ducted such a search, and his efforts were rewarded by the discovery that a 

 particular strain of Streptomyces olivaceus when grown under appropriate 



