He was "a pioneer in research on the elucidation and regulation of the biosynthetic pathways leading to the penicillins and cephalosporins" and "instrumental in the development of the beta-lactam industry".
[4][6][7] Demain attended Michigan State briefly, then joined the U.S. Navy in 1945 and spent two years in Philadelphia caring for amputees who were members of the armed forces who had been injured in the war.
His master's research topic was the spoilage and softening of pickles during fermentation, a phenomenon that, he concluded, was probably caused by pectic enzymes.
[6] From MSC, Demain went to the University of California's Department of Food Science, which was first at the Berkeley campus and then at Davis working with Herman Phaff.
Demain said that he and Phaff "apparently were the first in the world to carry out affinity chromatography, using a pectic acid gel to selectively adsorb YPG from culture filtrates.
[7] In early 1954, Demain moved to Danville, Pennsylvania, where he worked as a research microbiologist for Merck Sharp & Dohme, studying the synthesis of penicillin.
[4][6] In late 1955, Demain moved on to Merck's penicillin research laboratories in Rahway, New Jersey, where he worked on fermentation microbiology, â-lactam antibiotics, flavor nucleotides, and microbial nutrition.
[6] Demain named it the Department of Fermentation Microbiology[6] Demain "directed research and development on processes for monosodium glutamate, vitamin B12, streptomycin, riboflavin, cephamycin, fosfomycin, and interferon inducers,"[7] and "elucidated the mechanism by which the biosynthesis of cephalosporin in Cephalsporium acremonium was stimulated by the presence of methionine – a new mechanism which had not been reported before."
[4] In 1968, Demain was invited by Nevin Scrimshaw, head of the Department of Nutrition and Food Science at the Massachusetts Institute of Technology,[8] to become a full professor at that university.
The discovery of this enzyme established the role of penicillin as an intermediate in cephalosporin C biosynthesis and disproved the previous hypothesis that these two separate end products of C. acremonium were formed by a branched secondary metabolic pathway.
In his last MIT projects he studied Clostridium tetani and C. difficile with the aim of facilitating the production of improved tetanus and antibiotic-associated diarrhea vaccines.
[4] The August 2010 special issue of The Journal of Antibiotics celebrated Demain's career, noting that he had "established and maintained a renowned reputation within the field of industrial microbiology.