David Hopwood and the emergence of Streptomyce genetics

Abstract

Streptomyces spp. are unusual among bacteria in growing as mycelial colonies with sporulating aerial hyphae. They are very important as the source of most of the major antibiotics. Pioneering work by David Hopwood in the 1950s and 1960s established Streptomyces coelicolor A3(2) as the model system for the genus. Since then he has led successive key phases of research on this organism. In the 1970s, plasmids were discovered and characterised, and used both to establish conditions for transformation and in the subsequent development of cloning vectors. Protoplasts were exploited in both transformation and highly efficient cell fusion. In the 1980s, the early cloning of resistance genes from antibiotic-producing strains was followed by the cloning of antibiotic biosynthetic gene clusters, and the development of general methods and probes for the cloning of such clusters from diverse species. Analysis of these gene sets led to wide-ranging inferences about the biosynthesis of the important polyketide class of antibiotics, and to the production of hybrid antibiotics, and then, in the last decade, to more sophisticated combinatorial biosynthesis of designer molecules. In parallel, David Hopwood’s work has also provided a crucial platform for studies of the regulation of the morphological and physiological differentiation that is manifested by sporulating antibiotic-producing colonies. Most recently, his involvement in the physical mapping of the entire 8 Mb genome of S. coelicolor A3(2) has culminated in its complete DNA sequencing: a project that should be completed under his management during the year 2000.