David Hopwood | |
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Born | [1] | 19 August 1933
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Scientific career | |
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Thesis | Genetical and Cytological Studies on Actinomycetes (1973) |
Doctoral students | John Beringer [3] Mervyn Bibb [4] [5] Deng Zixin [6] |
Website |
Sir David Alan Hopwood FRS (born 19 August 1933) is a British microbiologist and geneticist. [1] [2] [7] [8]
Educated at Purbrook Park County High School and Lymm Grammar School, Hopwood gained his Bachelor of Arts degree from St John's College, Cambridge [1] and his PhD from the University of Glasgow in 1973. [9]
Hopwood served as an assistant lecturer in genetics at Cambridge until he became a Lecturer in Genetics at the University of Glasgow in 1961. [10] He later became John Innes Professor of Genetics at the University of East Anglia. He is now an Emeritus Fellow in the Department of Molecular Microbiology at the John Innes Centre. [10]
Hopwood was awarded the Gabor Medal in 1995 "in recognition of his pioneering and leading the growing field of the genetics of Streptomyces coelicolor A3(2), and for developing the programming of the pervasive process of polyketide synthesis". [11] In 2002, he co-authored the sequencing of the S. coelicolor A3(2) genome. [7] During more than forty years he has been studying the genetics and molecular biology of the model actinomycete S. coelicolor. [12]
Hopwood was elected a Fellow of the Royal Society in 1979 [13] and delivered their Leeuwenhoek Lecture in 1987. He is also the author of Streptomyces in Nature and Medicine: The Antibiotic Makers.
His nomination for the Royal Society reads:
Professor Hopwood has done outstanding work on the genetics of actinomycetes. He discovered genetic recombination of Streptomyces and developed original systems of genetic mapping which led him to the demonstration of a circular linkage group. This mapping work was important both in strengthening the generalization that the prokaryotes in general have circular chromosomes and in showing a tendency towards symmetry in the map suggestive of evolution by genome doubling. His electron microscope studies (with A. Glauert) showed beyond doubt the prokaryotic affinities of Streptomyces and demonstrated for the first time the existence of membranous "organelles" in continuity with plasma membrane. He has shown that the fertility system of Streptomyces coelicolor involves a sex factor associated with a plasmid. In the course of these studies he has discovered the first clear example of a plasmid-encoded antibiotics synthesis. Hopwood and his group have also extended the genetic analysis to other species of Streptomyces and Nocardia and demonstrated efficient DNA-mediated transformation to Thermoactinomyces. Current studies are directed towards the genetic analysis of development in S. coelicolor. While G. Semonti made some of the basic observations on recombination independently, Hopwood has been the prime mover in most of the advances. He now has an established international reputation as the leading pioneer and authority in what has become a very important aspect of microbial genetics. [14]
The Actinomycetota are a diverse phylum of Gram-positive bacteria with high G+C content. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to soil systems. In soil they help to decompose the organic matter of dead organisms so the molecules can be taken up anew by plants. While this role is also played by fungi, Actinomycetota are much smaller and likely do not occupy the same ecological niche. In this role the colonies often grow extensive mycelia, like a fungus would, and the name of an important order of the phylum, Actinomycetales, reflects that they were long believed to be fungi. Some soil actinomycetota live symbiotically with the plants whose roots pervade the soil, fixing nitrogen for the plants in exchange for access to some of the plant's saccharides. Other species, such as many members of the genus Mycobacterium, are important pathogens.
Streptomyces is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of Streptomyces bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, and have very large genomes with high GC content. Found predominantly in soil and decaying vegetation, most streptomycetes produce spores, and are noted for their distinct "earthy" odor that results from production of a volatile metabolite, geosmin. Different strains of the same species may colonize very diverse environments.
In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups: [−C(=O)−CH2−]n. First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity.
The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-positive and anaerobic and have mycelia in a filamentous and branching growth pattern. Some actinomycetes can form rod- or coccoid-shaped forms, while others can form spores on aerial hyphae. Actinomycetales bacteria can be infected by bacteriophages, which are called actinophages. Actinomycetales can range from harmless bacteria to pathogens with resistance to antibiotics.
The avermectins are a series of drugs and pesticides used to treat parasitic worm infestations and to reduce insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. Eight different avermectins were isolated in four pairs of homologue compounds, with a major (a-component) and minor (b-component) component usually in ratios of 80:20 to 90:10. Avermectin B1, a mixture of B1a and B1b, is the drug and pesticide abamectin. Other anthelmintics derived from the avermectins include ivermectin, selamectin, doramectin, eprinomectin.
Aminocoumarin is a class of antibiotics that act by an inhibition of the DNA gyrase enzyme involved in the cell division in bacteria. They are derived from Streptomyces species, whose best-known representative – Streptomyces coelicolor – was completely sequenced in 2002. The aminocoumarin antibiotics include:
6C RNA is a class of non-coding RNA present in actinomycetes. 6C RNA was originally discovered as a conserved RNA structure having two stem-loops each containing six or more cytosine (C) residues. Later work revealed that 6C RNAs in Streptomyces coelicolor and Streptomyces avermitilis have predicted rho-independent transcription terminators, and microarray and reverse-transcriptase PCR experiments indicate that the S. coelicolor version is transcribed as RNA. Transcription of the S. coelicolor RNA increases during sporulation, and three transcripts were detected that overlap the 6C motif, but have different apparent start and stop sites.
Streptomyces griseus is a species of bacteria in the genus Streptomyces commonly found in soil. A few strains have been also reported from deep-sea sediments. It is a Gram-positive bacterium with high GC content. Along with most other streptomycetes, S. griseus strains are well known producers of antibiotics and other such commercially significant secondary metabolites. These strains are known to be producers of 32 different structural types of bioactive compounds. Streptomycin, the first antibiotic ever reported from a bacterium, comes from strains of S. griseus. Recently, the whole genome sequence of one of its strains had been completed.
Actinorhodin is a benzoisochromanequinone dimer polyketide antibiotic produced by Streptomyces coelicolor. The gene cluster responsible for actinorhodin production contains the biosynthetic enzymes and genes responsible for export of the antibiotic. The antibiotic also has the effect of being a pH indicator due to its pH-dependent color change.
Valine dehydrogenase (NAD+) (EC 1.4.1.23) is an enzyme with systematic name L-valine:NAD+ oxidoreductase (deaminating). This enzyme catalyses the following chemical reaction
Streptomyces isolates have yielded the majority of human, animal, and agricultural antibiotics, as well as a number of fundamental chemotherapy medicines. Streptomyces is the largest antibiotic-producing genus of Actinomycetota, producing chemotherapy, antibacterial, antifungal, antiparasitic drugs, and immunosuppressants. Streptomyces isolates are typically initiated with the aerial hyphal formation from the mycelium.
Mervyn James Bibb is an Emeritus Fellow at the John Innes Centre, Norwich, UK.
Streptomyces albidoflavus is a bacterium species from the genus of Streptomyces which has been isolated from soil from Poland. Streptomyces albidoflavus produces dibutyl phthalate and streptothricins.
Streptomyces lavendulae is a species of bacteria from the genus Streptomyces. It is isolated from soils globally and is known for its production of medically useful biologically active metabolites. To see a photo of this organism click here.
Streptomyces glaucescens is a bacterium species from the genus of Streptomyces which has been isolated from soil. Streptomyces glaucescens produces tetracenomycin C, tetracenomycin D and tetracenomycin E.
Streptomyces phaeochromogenes is a bacterium species from the genus of Streptomyces. Streptomyces phaeochromogenes produces tyrosinate, bromoperoxidase, ditryptophenalin, phaeochromycin A, phaeochromycin B, phaeochromycin C, phaeochromycin D and phaeochromycin E. Streptomyces phaeochromogenes also produces moenomycin and bambermycin.
Streptomyces virginiae is a bacterium species from the genus of Streptomyces which has been isolated from soil. Streptomyces virginiae produces actithiazic acid, virginiamycins and cycloserine. Streptomyces virginiae also produces monensin A, monensin B, monensin C, monensin D, actithiazic acid.
Streptomyces viridosporus is a bacterium species from the genus of Streptomyces. Streptomyces viridosporus produces sistomycine and lignin peroxidase. Streptomyces viridosporus can degrade lignin and humic acids. Streptomyces viridosporus also produces moenomycin A, a component of bambermycin.
A jadomycin is a natural product produced by Streptomyces venezuelae ISP5230 (ATCC10712), the organism which is most well known for making the antibiotic chloramphenicol. The name jadomycin is applied to a family of related angucyclines which are distinguished by the E ring, which is derived from an amino acid. The amino acid incorporation which forms the E-ring is a chemical reaction, rather than enzymatic, an uncommon occurrence in biosynthesis. As such a number of jadomycins incorporating different amino acids have been discovered. Jadomycin A was the first compound of this family to be isolated and constitutes the angucylic backbone with L-isoleucine incorporated into the E-ring. A related analog, jadomycin B, is modified by glycosylation with a 2,6-dideoxy sugar, L-digitoxose. Jadomycins have cytotoxic and antibacterial properties.
Genome mining describes the exploitation of genomic information for the discovery of biosynthetic pathways of natural products and their possible interactions. It depends on computational technology and bioinformatics tools. The mining process relies on a huge amount of data accessible in genomic databases. By applying data mining algorithms, the data can be used to generate new knowledge in several areas of medicinal chemistry, such as discovering novel natural products.