Pickles, Pectin, and Penicillin

Abstract

■ Abstract My professional life has been devoted to the study of microbial products and their biosynthesis, regulation, and overproduction. These have included primary metabolites (glutamic acid, tryptophan, inosinic acid, guanylic acid, vitamin B 12 , riboflavin, pantothenic acid, ethanol, and lactic acid) and secondary metabolites (penicillin, cephalosporins, streptomycin, fosfomycin, gramicidin S, rapamycin, indolmycin, microcin B17, fumagillin, mycotoxins, Monascus pigments, and tetramethylpyrazine). Other areas included microbial nutrition, strain improvement, bioconversions of statins and β-lactams, sporulation and germination, plasmid stability, gel microdroplets, and the production of double-stranded RNA, the polymer xanthan, and enzymes (polygalacturonase, protease, cellulase). Most of the studies were carried out with me by devoted and hardworking industrial scientists for 15 years at Merck & Co. and by similarly characterized students, postdoctorals, and visiting scientists during my 32 years at the Massachusetts Institute of Technology. I owe much of my success to my mentors from academia and industry. My recent research activities with undergraduate students at the Charles A. Dana Research Institute for Scientists Emeriti (R.I.S.E.) at Drew University have been very rewarding and are allowing me to continue my career. CONTENTS

Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence β-lactams)

“…The material was not well characterized (e.g., as 6-APA) and there was some controversy. However, Kato's claim was fully confirmed by A. Demain in 1955 [20].…”

Arnold Lester Demain: a good friend, an outstanding scientist and a valuable professor

“…In 2004, Dr Demain was given the honor of presenting his autobiography as the introductory chapter of the Annual Reviews of Microbiology. 8 Of course, he called it 'Pickles, pectin, and penicillin' , and now, in 2010, this special issue of the Journal of Antibiotics is being dedicated to Arny Demain. Here, he contributed with his own paper entitled 'Antimicrobial spectrum of the antitumor agent, cisplatin' .…”

Production of biofuels and biochemicals by in vitro synthetic biosystems: Opportunities and challenges

“…Although Eduard Buchner discovered the phenomenon of cell-free ethanol fermentation in the 1890s, the use of one purified enzyme along with enzyme immobilization for industrial production began in the 1960s-1970s, for example, high fructose corn syrup (i.e., more than 10 billion US dollars yearly) and semi-synthetic antibiotics (e.g., cephalosporin) (Demain, 2004). Such cell-free systems evolved to more complicated onesmulti-enzyme one pot for enhancing volumetric productivity, decreasing product inhibition, and shifting reaction equilibrium (Santacoloma et al, 2010;Schoffelen and van Hest, 2012).…”