Professor Robert Thomas M蜜桃社区
1927 - 2018
Bob Thomas was born in Edinburgh on 21 February 1927. He was educated at Emmanuel Boys School, London, and then at the University of London in a Special Two-Year Degree in Chemistry. He began his PhD studies in 1947 at the London School of Hygiene and Tropical Medicine under the supervision of Professor Harold Raistrick, a UK pioneer in the study of microbial metabolites. Working on metabolites of the mould, Alternaria tenuis, Bob isolated two new crystalline compounds and unambiguously elucidated the structure of one of them, alternariol, showing the other to be one of two possible monomethyl ethers of alternariol.
In January 1952 he married Joan Barron and they set sail for Melbourne where Bob took up an appointment as a Senior Research Officer with the Commonwealth Scientific and Industrial Research Organisation's Protein Chemistry Laboratory and commenced a study of the degradation of cellulose by fungal enzymes. He continued to work in this area on moving to a post at the National Research Council, Ottawa, where he spent most of 1955.
At the beginning of his time in Melbourne, he had attended a lecture by Arthur Birch who was on his way from Cambridge to take up the Chair of Chemistry at The University of Sydney. This lecture was on the proposal that many polyketide natural products are biosynthesised from linear chains of two-carbon units derived from acetate. Bob recognised during the lecture that alternariol could be formed from seven acetate units (a heptaketide) and after the lecture he discussed its structure (then unpublished) with Birch. Birch invited him to join him in Sydney to work on testing the polyketide hypothesis by feeding studies with acetate. Although tempted, he was only two months into his job with CSIRO and felt that he could not jump ship. However this meeting sparked a lifelong interest in biosynthesis in general and of polyketides in particular.
In early 1956 he returned to the London School of Hygiene and Tropical Medicine to take up an ICI Fellowship and began an investigation of the biosynthesis of alternariol using 14C-labelled acetate. His next move, in 1959, was to join the Squibb Institute for Medical Research, New Jersey where he stayed for four years, investigating the biosynthesis of various antibiotics and also indole alkaloids. He returned to the UK in 1963 to take up a Senior Lectureship at Imperial College in Professor Ernst Chain's Biochemistry Department. This was not an enjoyable time for him as he was largely constrained to work on Chain's projects rather than his own, as was his entitlement as an independent member of staff. Fortunately, the University of Surrey offered him a position as Research Professor of Chemistry in 1969, a post which he accepted with alacrity! While there he set up and became Founding Director of the Biotechnology Unit. He launched the biotechnology company Biotics Ltd in 1983 and in 1987 at age 60 he took up an Honorary Professorship at the University of Sussex.
Independent Research and Publication
Bob began his independent work in 1956 at the London School of Hygiene and Tropical Medicine and over the next 5 years published a series of papers entitled Studies in the Biosynthesis of Fungal Metabolites. This embraced studies of several classes of fungal metabolites among which were phenalenones such as herquinone as well as alternariol and its congeners. The studies involved feeding 14C-labelled precursors such as acetate, mevalonate and simple aromatic phenolic compounds to microorganisms and isolating the labelled metabolites. Chemical degradation then established the distribution of the radiocarbon labels in these compounds. In addition to the biosynthetic work ultimate proof of structure by synthesis was accomplished for several metabolites. The structures of some of the metabolites that he isolated resisted characterisation and were only solved in the 1970s when modern methods such as NMR spectroscopy and mass spectrometry were more generally used. As a result, publication of the structures of mould metabolites continued right up to his retirement, the final ones being published in collaboration with a German research group in 2016/18.
Over the years Bob contributed immensely to biosynthetic theory and his speculative ideas have been proved by experiment. The indole alkaloids are a large and important class of natural products including strychnine, yohimbine and corynanthine and speculation on their biosynthetic origin has abounded, with such luminaries as Sir Robert Robinson, R B Woodward and others making what appeared to be reasonable hypotheses as to their origin. It was however Bob's suggestion in 1961 that a cyclopentanoid monoterpene was involved in the biosynthesis that led to the final correct biosynthesis being proved experimentally in three simultaneous publications by the research groups of Arigoni, Scott and Battersby.
His longstanding interest in polyketides also led him to be the first to suggest that tetracyclic aromatic polyketides may be formed by two possible types of folding, one of which occurs in streptomyces and the other in fungi. These S- and F-foldings can be identified by feeding studies with [1,2-13C]-acetate. His recognition of the subtle difference in the two phyla has permitted some reassignments of natural product structures and no example has yet been found that contradicts the 'Thomas Rule'.
The biosynthesis of penicillins and cephalosporin has excited the interest of many groups over the years, and in 1981, while at Surrey, Bob and his research group were able to make a significant experimental contribution to this work. It had been known that the basic skeleton of these beta-lactam antibiotics was derived from the amino acids L-cysteine and L-valine with inversion of stereochemistry of the latter to D-valine before incorporation into a precursor tripeptide. There were two possible mechanisms for the incorporation of the valine carboxyl unit of the tripeptide into the final antibiotic and Bob used [18O2]-L-valine to show that one of the two isotopically labelled oxygen atoms in this carboxyl group was lost in conversion to penicillin V, suggesting the intermediacy of a nonribosomal thioester.
In 1974, while at Surrey, he was among the first to employ tritium NMR to study biosynthetic problems and this enabled him to demonstrate the locations of the labelled tritons (protons) in biosynthetic products unambiguously. He identified dehydrogenation in ring A of testosterone as being a stereospecific trans elimination and showed that some polyketides incorporated [3H]-acetate to yield label located in the expected positions. This was a useful advance for, in certain examples, it provided information not available from incorporation studies using deuterium-labelled precursors.
In studies using [1,2-13C]- and [1-13C,2H3]-acetate and assay by 13C NMR he demonstrated, respectively, that the tetracyclic skeleton of oxytetracycline was derived from a linear polyketide and that both of the deuterium (hydrogen) atoms in its aromatic A-ring were labelled as would be expected from their polyketide origin. Further, he showed using [1-13C,18O2]-acetate that the expected regiospecific locations of the 18O-oxygen substituents in oxytetracycline corresponded exclusively to those oxygen-bearing carbons that originated biosynthetically from the carboxyl group of acetate.
He published over 60 research papers, completing his last work in his 91st year in collaboration with a German group. This was published posthumously. He wrote several reviews and co-edited three multi-author books from the three UK natural product meetings that he organised.
Business Interests
In 1983, while Director of the Biotechnology Unit at the University of Surrey, Bob started up a new company, Biotics, at first as a Biotechnology Consultancy specialising in the area of natural product chemistry. However, with the aid of a grant from the European Commission he was able to begin its main activity that of setting up a laboratory facility in the School of Chemistry and Molecular Sciences at the University of Sussex to isolate new compounds from plants from all over the world. Once a standardised protocol for the extraction of plant material had been accomplished (formalised in a spin-off company, Bioex), the most important development was setting up a series of individual companies in developing countries in Africa, Asia and South America to duplicate what was being done at Sussex, with the important aim that each country (aBiotex Associate) would directly benefit from any discoveries made. Biotics would provide consultancy and technical support services and act as broker between them and individual pharmaceutical and agrochemical companies who, after screening the extracts for bioactivity, might wish to commercialise any of the discovered compounds. By the mid-1990s extraction facilities had been established in Costa Rica, Ghana and Indonesia and more than 5,000 samples had been screened.
Contributions to the 蜜桃社区 (蜜桃社区)
In his role at Surrey as Director of the Biotechnology Unit, it was natural for Bob to join the Biotechnology Group, a new 蜜桃社区 Interest Group which started up in 1987. He became a member of the inaugural Committee and subsequently was to serve as its Treasurer for 10 years, 1995/2004. He chaired the organising committee for the first 3-Day conference that the Group had ever run and this was on the theme of natural products at the University of Sussex in 1996. He followed this up with two more on the same theme at St Andrews in 1999 and at Magdalen College, Oxford in 2009.
Outside Interests
Bob learned to fly in the University of London Air Squadron in 1947 and joined the RAF Volunteer Reserve. While in Melbourne he joined the RAAF Volunteer Reserve. Flying was to be a lifelong interest and he even piloted a light aircraft when he was 89! He was an excellent squash and tennis player, enjoying games with colleagues at the Sussex campus until well into his seventies.
Family and Friends
Outside of work, Bob was a devoted husband and father. In later life he was a loving grandfather and great grandfather, too.
Bob Thomas had many scientific and other friends from all over the world, partly from his overseas jobs and partly from his travels lecturing at and organising international conferences.
His wife, Joan died in 2011 but he is survived by his three children Russell, Julie and Jacki, seven grandchildren and one great grandchild.
Colin T. Bedford and Douglas W. Young
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