Saul Roseman: His many contributions to biochemistry over eight decades

Saul Roseman (born 1921) was the Ralph S. O'Connor Professor of Biology, Emeritus, at The Johns Hopkins University. He died of congestive heart failure on July 2, 2011 at the age of 90.

Saul Roseman.

Roseman was born in Brooklyn and received his bachelor's degree in Chemistry from the City College of New York (CCNY) in 1941, one of a remarkable number of scientists of his generation to receive their science training at CCNY. He began graduate training in Biochemistry at the University of Wisconsin only to have it interrupted by service in the infantry in Europe in World War II, also common for young men of his generation. After the war, he completed his PhD studies in 1948 with Karl Paul Link, discoverer of the anticoagulant coumarin. Roseman examined the metabolic products of dihydroxy courmarin metabolism found in dog urine and discovered that the secreted products were modified with glucuronide and glucuronic acid derivatives. This finding was the beginning of his distinguished career as a glycobiologist, which would grow in many often unexpected directions or as Roseman was fond of saying, “serendipitous turns,” and his pathway was set.

As a postdoctoral fellow at the University of Chicago with Albert Dorfman, also just returned from the war, Roseman continued work on complex carbohydrates and developed methods for radioisotope metabolic studies for biosynthesis of hyaluronic acid and chondroitin sulfate. He synthesized radiolabeled glucose (there were no supply companies) and used it to show that hyaluronic acid synthesized by Streptococcus contained radiolabel in both the glucosamine and glucuronic acid without any scission of the carbon skeleton of glucose.

He began his independent academic career as an Assistant Professor of Biochemistry and a member of the Rackham Arthritis Research Unit at the University of Michigan, and he rose through the professorial ranks in his 11 years at Michigan. This period marks a hallmark in his career, because he, with postdoctorate student Donald Comb, elucidated the structure of N-acetylneuraminic acid, one of the sialic acids. The structures of the sialic acids had been quite controversial, and over a period of three decades, at least 11 structures had been proposed. Comb and Roseman used meticulous enzymology and chemistry that helped establish the correct structure (1). They also discovered the sugar nucleotide CMP sialic acid and showed that it is the sialyl donor of glycosyltransferases for synthesis of many of the complex oligosaccharides comprising glycoproteins and glycolipids.

In a serendipidous change of course, Roseman's group was examining the biosynthesis of colominic acid, a homopolymer of sialic acid in some strains of Escherichia coli, and they discovered a novel sugar kinase system that used phosphoenolpyruvate (PEP) as the phosphoryl donor rather than ATP. Careful study of this system determined that the kinase activity involved complex enzymology of three proteins, termed Enzyme I, HPr, and Enzyme II, and in some bacteria, there was an additional protein, Factor III. The pathway involves a series of phosphotransfer reactions, with the phosphate of PEP transferred sequentially to each of the three to four proteins and ending up on the sugar. Although Enzyme I and HPr are soluble proteins, Enzyme II was bound to the bacterial membrane. This observation and subsequent genetic studies established that this system, now called the PEP glycose phosphotransferase system (PTS), is responsible for the transport of sugars across the bacterial membrane with concomitant phosphorylation. This system not only affects membrane passage but also initiates the first step in sugar metabolism. Dozens of different sugars and sugar alcohols are transported by the PTS in dozens of different bacteria.

In the later stages of his career and until the time of his death, he returned to the metabolism of hexosamines and studied chitin, a polymer of N-acetylglucosamine and the second most abundant organic compound in nature (second only to cellulose). It is found as the exoskeletal structural component of arthropods, including insects and crustacea like crabs and lobsters. In the oceans, degradation of this highly insoluble polymer by marine bacteria like Vibrio sp. removes and recycles chitin components as part of the balance of nature in the ocean.

Roseman published many of his papers, often five at a time, in the Journal of Biological Chemistry (JBC). JBC now features the seminal work of many distinguished biochemists in JBC Classics, which are papers reprinted along with biographical information about the author. Roseman has a unique standing with four papers in JBC Classics: a paper published as a graduate student with Karl Paul Link (2), a paper published as a postdoctorate student with Albert Dorfman (3), and two papers published as an independent scientist (1, 4). He had notable success at every stage of his remarkable career.

Any characterization of Roseman's career that is limited to his scientific contributions is incomplete, because he was equally remarkable and far more complex as a person. He was a mentor to over 100 students and postdoctorate students, and he set very high standards for scientific rigor. He was diligent about promoting the careers of those people who had worked with him. There are countless anecdotes about applying high standards to the work of others and especially, to those people within his own group. Identification of an unknown compound by paper chromatography would require, at the very least, comigration with the known sample in at least five different solvents. The people fortunate to have received training in his laboratory experienced weekly laboratory meetings, always held on Monday evening, at which each laboratory member would, in turn, present their recent work to the rest of the group with constructive and occasionally, withering critique. This meeting served as a model for his trainees, because many went on to run laboratories of their own. The weekly laboratory meetings were sacrosanct, and little short of death warranted an excused absence. They were sacrosanct, that is, until the advent of Monday night football on television. This scheduling presented a huge conflict for Roseman, because he was a devoted football fan, and missing Monday night football for laboratory meetings was a test. Laboratory meetings won! He was a special fan of the Baltimore Colts and was most distressed, along with all of Baltimore, when the Colts moved to Indianapolis. He was slow to warm to the replacement Baltimore Ravens but eventually succumbed.

Roseman was also an avid sailor, taking advantage of the great opportunities for adventure that the Chesapeake Bay had to offer. Soon after moving from Michigan to Baltimore, he bought a sail boat from a colleague and having never sailed before, started to take lessons with the same seriousness and commitment that he had for research. It took some time (actually, a long time), but eventually, he and his wife Martha enjoyed sailing the Bay. However, to those people familiar with his sailing escapades, there were also many anecdotes.

Roseman was devoted to his family: his wife Martha, who died of cancer a few weeks after Roseman's death, their 3 children Mark, Dorinda, and Cynthia, 7 grandchildren, and 11 great grandchildren. He was also devoted to the over 100 students and postdoctorate students who comprised his scientific family and whose lives and careers he helped promote and shape.

Roseman received many honors for his work. He was elected to the National Academy of Sciences (1972). He received the Rosensteil Award from Brandeis University (1974), the International Award from the Gairdner Foundation (1981), and the Karl Meyer Award from the Society for Glycobiology. He was a force of nature, with infectious enthusiasm and delightful humor. He will be sorely missed.