Streptomyces species belong to the branch of Gram-positive bacteria known as actinomycetes that are characterised by a high G+C content in their DNA. They are used to produce the majority of antibiotics used in human and veterinary medicine and agriculture, as well as anti-parasitic agents, herbicides, pharmacologically active metabolites (e.g. immuno-suppressants) and several enzymes important in the food and other industries. Streptomyces are also unusual amongst bacteria in their mycelial, sporulating life cycle, which involves complex regulation of gene expression in space and time. The Streptomyces research groups at the John Innes Centre (JIC), led by Mervyn Bibb, Mark Buttner and Michael McArthur and the University of East Anglia (UEA), led by Matt Hutchings and Gabriela Kelemen, are seeking to understand their genetics, molecular biology and physiology and to discover new species and new antibiotics from unusual environmental niches.

Streptomyces coelicolor

Genetics, genomics and functional genomics: Numerous Streptomyces genomes have now been sequenced, the first of which was Streptomyces coelicolor, the model organism for the genus. The S. coelicolor genomewas sequenced at the Wellcome Sanger Centre in Cambridge in collaboration with the JIC. Several complete Streptomyces genome sequences can be viewed in the StrepDB database which has been established at the JIC by Dr. Govind Chandra. More recently the Genome Analysis Centre, which is also on the Norwich Research Park, has produced draft genome sequences of several fungus-farming ant-associated Streptomyces species in collaboration with Matt Hutchings (UEA) and Mervyn Bibb (JIC).

Antibiotic biosynthesis: We are studying the organization and pathway-specific regulation of biosynthetic gene clusters in the model organism S. coelicolor and in other Streptomyces species; we are developing techniques to unlock silent pathways in Streptomyces species in an effort to discover new antibiotics; we are using Streptomyces as heterologous hosts to express biosynthetic gene clusters from other actinomycetes; and we are investigating fungus-farming insects as a potential source of new Streptomyces species and new antibiotics.

Morphological differentiation: This complex process is being studied in both Streptomyces coelicolor and Streptomyces venezuelae. We are using microarray and ChIP-chip to study the functions, interactions and spatial and temporal expression of regulatory genes controlling aerial mycelium formation and the metamorphosis of aerial hyphae into spore chains; the modifications of cell division processes that lead into sporulation; the organisation of the hyphal tip; and the significance of the synthesis of sporulation-associated proteins and pigments at specific times and cellular locations.

Stress responses: Many of the unexpectedly large number (>65) of RNA polymerase sigma factors and two-component systems (>84) in S. coelicolor are likely to be involved in responses to environmental changes. We have made recent progress particularly in analysing responses to redox, nitrosative and cell envelope stress.

Selected references:

Den Hengst CD, Tran NT, Bibb MJ, Chandra G, Leskiw BK and Buttner MJ (2010). Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol doi:10.1111/j.1365-2958.2010.07338.x

Barke J, Seipke RF, Grüschow S, Heavens D, Drou N, Bibb MJ, Goss RJ, Yu DW, Hutchings MI (2010). A mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus. BMC Biol 8:109.

Flardh K and Buttner MJ (2009). Streptomyces morphogenetics: dissecting differentiation in a filamentous bacterium. Nat Rev Microbiol 7:36-49.

McArthur M and Bibb MJ (2008). Manipulating and understanding antibiotic production in Streptomyces coelicolor A3(2) with decoy oligonucleotides. Proc Natl Acad Sci U S A 105:1020-5.

Dalton KA, Thibessard A., Hunter JI and Kelemen GH (2007). A novel compartment, the 'subapical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor. Mol Microbiol 64:719-37.

Institute of Food ResearchJohn Innes CentreSainsbury LabThe Genome Analysis CentreUniversity of East Anglia