Abstract
Actinomycetes produce about two-thirds of all known antibiotics of microbial origin, and remain an important source of potentially clinically useful compounds. These include ribosomally synthesised and post-translationally modified peptides (RiPPs). Using genome mining, we have isolated and characterised gene clusters responsible for the biosynthesis of the RiPPs cinnamycin, microbisporicin, cypemycin, venezuelin, bottromycin and planosporicin. This presentation will describe experiments that have revealed novel regulatory mechanisms, a novel mechanism of immunity, and a crucial role for immunity in regulating the onset of antibiotic biosynthesis; evidence will also be presented that suggests that at least some RiPPs serve as signalling molecules to induce their own synthesis.
Biography
Mervyn Bibb obtained a BSc (1st Class) in Genetics and Developmental Biology from the University of East Anglia (UEA) (1974) and a PhD from UEA/John Innes Centre (JIC) (1977) in Streptomyces genetics working under the supervision of Prof Sir David Hopwood FRS. He then worked as a NATO postdoctoral research fellow (1978-1982) in the laboratory of Prof Stanley Cohen at Stanford University, CA, USA. In 1982 he took up a faculty position at JIC, and served as Head of the Department of Molecular Microbiology in 2000, and between 2004 and 2009. He served as Senior Research Director for Natural Product Discovery, Diversa Corporation (now Verenium, BASF), San Diego, USA during a leave of absence from JIC between 2001- 2003.
Mervyn Bibb’s research focuses on the antibiotic biosynthesis in actinomycetes, Gram-positive terrestrial and marine bacteria that produce about two-thirds of all known antibiotics of microbial origin, many of which are used clinically. He has a particular interest in lantibiotics (modified peptide antibiotics) produced by Streptomyces, Actinoplanes, Microbispora and Planomonospora species. He has been intimately involved in genome sequencing (he led the project to determine the genome sequences of Streptomyces venezuelae and Streptomyces leeuwenhoekii), and more recently has applied genome sequencing and genomic approaches to isolate gene clusters for a variety of unusual antibiotics, several of which lacked biosynthetic precedents. The resulting knowledge is used not only to understand how these complex molecules are made, but also to engineer the producing organisms to make potentially improved derivatives. He has published 180 papers and presented the work of his group at over 70 international conferences. He is the recipient of the Lepetit Award, the Colworth Prize, the Charles Thom Award and the Norman Heatley Medal for his work on antibiotic biosynthesis. He is an Honorary Professor at UEA Norwich, Imperial College London, and the Institute of Microbiology, Chinese Academy of Sciences, Beijing. He is also a Fellow of the Royal Society, the American Academy of Microbiology and of the Royal Society of Chemistry. Work in his group led to the formation of two JIC spin-out companies, Novacta Biosystems (which has a lantibiotic derivative about to enter Phase II clinical trials for Clostridium difficile infections) and Procarta Biosystems, of which he is co-founder (Procarta are developing a novel approach to anti- infective treatment applicable to both Gram-positive and Gram-negative infections).