Sphingolipid biosynthesis in man and microbes
A new review covering up to 2018 Sphingolipids are essential molecules that, despite their long history, are still stimulating interest today. The reasons for this are that, as well as playing structural roles within cell membranes, they have also been shown to perform a myriad of cell signalling fu...
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| Published in | Natural product reports Vol. 35; no. 9; pp. 921 - 954 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
19.09.2018
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| Subjects | |
| Online Access | Get full text |
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| Summary: | A new review covering up to 2018
Sphingolipids are essential molecules that, despite their long history, are still stimulating interest today. The reasons for this are that, as well as playing structural roles within cell membranes, they have also been shown to perform a myriad of cell signalling functions vital to the correct function of eukaryotic and prokaryotic organisms. Indeed, sphingolipid disregulation that alters the tightly-controlled balance of these key lipids has been closely linked to a number of diseases such as diabetes, asthma and various neuropathologies. Sphingolipid biogenesis, metabolism and regulation is mediated by a large number of enzymes, proteins and second messengers. There appears to be a core pathway common to all sphingolipid-producing organisms but recent studies have begun to dissect out important, species-specific differences. Many of these have only recently been discovered and in most cases the molecular and biochemical details are only beginning to emerge. Where there is a direct link from classic biochemistry to clinical symptoms, a number a drug companies have undertaken a medicinal chemistry campaign to try to deliver a therapeutic intervention to alleviate a number of diseases. Where appropriate, we highlight targets where natural products have been exploited as useful tools. Taking all these aspects into account this review covers the structural, mechanistic and regulatory features of sphingolipid biosynthetic and metabolic enzymes.
Sphingolipids are found in nearly all domains of life where they play a myriad of essential roles in structure and signalling. This review covers recent highlights from studies of the structures, mechanisms and inhibitors of key enzymes from the sphingolipid biosynthetic enzymes of prokaryotes and eukaryotes. |
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| Bibliography: | Dominic Campopiano is Chair of Industrial Biocatalysis in the School of Chemistry at the University of Edinburgh. He studied chemistry at the University of Glasgow (1984-88) then carried out his PhD studies in Chemistry at the University of Edinburgh under the supervision of Prof. Robert L. Baxter (1988-91). After post-doctoral stints with Prof. Bill Shaw in Biochemistry at the University of Leicester and in Chemistry at Edinburgh, he was appointed to a lectureship in 1995. He was promoted through the ranks of senior lecturer and reader before taking up his chair in 2015. He has an interest in natural product biosynthesis and exploiting the enzymes that catalyse their production. He has collaborated with a number of crystallographers to investigate the structures and mechanisms of key enzymes from sphingolipid, antibiotic and vitamin biosynthetic pathways. Teresa Dunn is Professor and Chair of Biochemistry and Molecular Biology at the Edward Herbert School of Medicine, Uniformed Services University of the Health Sciences (USUHS) in Bethesda, MD. She received her B.S. in Biochemistry from the University of Maine at Orono in 1978 and her Ph.D. in Biochemistry from Brandeis University in 1984. Following a postdoctoral fellowship in the Department of Biological Chemistry at the Johns Hopkins University School of Medicine (1984-1988), she joined the faculty at USUHS. Her research group has been focused on the identification, function, regulation and structure of enzymes of the sphingolipid biosynthetic pathway for nearly thirty years. Peter Harrison completed his MChem degree in Chemical Biology at the University of Warwick in 2011. He then stayed at Warwick to complete his PhD under the supervision of Prof. Tim Bugg, where his research focused on the enzymology of carotenoid cleavage dioxygenase enzymes in plant hormone biosynthesis. In 2015 he moved to the University of Edinburgh to work with Prof. Dominic Campopiano on the structural characterisation of sphingolipid biosynthesis enzymes, in particular of serine palmitoyltransferase. He is currently a postdoctoral researcher in the group of Prof. Jim Naismith in Harwell, Oxford. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
| ISSN: | 0265-0568 1460-4752 |
| DOI: | 10.1039/c8np00019k |