My major interest is the regulation of secondary metabolism, particularly antibiotic production, in Streptomyces coelicolor and Streptomyces venezuelae, and its growth phase-dependence. A variety of molecular and genetic techniques, including global transcriptome and proteome analysis, are being applied to analyse the expression of gene clusters encoding several of the secondary metabolites made by these strains.
The influence of growth rate, intracellular ppGpp and extracellular signalling molecules on the expression of pleiotropic and pathway-specific regulatory genes are studied to elucidate regulatory networks and the underlying mechanisms of signal transduction.
The recent sequencing of the complete genomes of several streptomycete species revealed the presence of a large number of "cryptic" secondary metabolic gene clusters, and led to the realisation that these organisms have the ability to produce many more natural products than had previously been recognised. One of the aims of this work is to identify the physiological signals and regulatory mechanisms responsible for the activation of these "cryptic" pathways, thus unleashing the full biosynthetic potential of these prodigious producers of valuable natural products. These studies are now being extended to include other "rare" actinomycete species.
I am also interested in an unusual class of peptide antibiotics (lantibiotics) made by streptomycetes and other high G+C actinomycetes. Work is in progress to understand the biosynthesis of the lantibiotic cinnamycin made by Streptomyces cinnamoneus, to isolate gene clusters encoding novel lantibiotics, and to use recombinant approaches to generate novel peptides with valuable pharmaceutical and agricultural applications.
I recently served as Senior Research Director at Diversa Corporation in San Diego, where I directed the establishment of a small molecule discovery program based on the use of a proprietary streptomycete that was used to express heterologous secondary metabolic gene clusters. Both micro-array and global proteome analyses were employed to improve this organism as an expression host for the production of small molecules.
Gomez-Escribano J. P., Bibb M. J. (2014)
Heterologous expression of natural product biosynthetic gene clusters in Streptomyces coelicolor: from genome mining to manipulation of biosynthetic pathways.
Journal of Industrial Microbiology & Biotechnology 41 (2) 425-31
Arnison P. G., Bibb M. J., Bierbaum G., Bowers A. A., Bugni T. S., Bulaj G., Camarero J. A., Campopiano D. J., Challis G. L., Clardy J., Cotter P. D., Craik D. J., Dawson M., Dittmann E., Donadio S., Dorrestein P. C., Entian K. D., Fischbach M. A., Garavelli J. S., Göransson U., Gruber C. W., Haft D. H., Hemscheidt T. K., Hertweck C., Hill C., Horswill A. R., Jaspars M., Kelly W. L., Klinman J. P., Kuipers O. P., Link A. J., Liu W., Marahiel M. A., Mitchell D. A., Moll G. N., Moore B. S., Müller R., Nair S. K., Nes I. F., Norris G. E., Olivera B. M., Onaka H., Patchett M. L., Piel J., Reaney M. J., Rebuffat S., Ross R. P., Sahl H. G., Schmidt E. W., Selsted M. E., Severinov K., Shen B., Sivonen K., Smith L., Stein T., Süssmuth R. D., Tagg J. R., Tang G. L., Truman A. W., Vederas J. C., Walsh C. T., Walton J. D., Wenzel S. C., Willey J. M., van der Donk W. A. (2013)
Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.
Natural Product Reports 30 (1) 108-60
Holley T. A., Stevenson C. E., Bibb M. J., Lawson D. M. (2013)
High resolution crystal structure of Sco5413, a widespread actinomycete MarR family transcriptional regulator of unknown function.
Proteins: Structure, Function, and Bioinformatics 81 (1) 176-82
Jones A. C., Gust B., Kulik A., Heide L., Buttner M. J., Bibb M. J. (2013)
Phage P1-derived artificial chromosomes facilitate heterologous expression of the FK506 gene cluster
PLoS One 8 (7) e69319
Sherwood E. J., Bibb M. J. (2013)
The antibiotic planosporicin coordinates its own production in the actinomycete Planomonospora alba.
Proceedings of the National Academy of Sciences of the United States of America 110 (27) E2500-E2509
Sherwood E. J., Hesketh A. R., Bibb M. J. (2013)
Cloning and Analysis of the Planosporicin Lantibiotic Biosynthetic Gene Cluster of Planomonospora alba.
Journal of Bacteriology 195 (10) 2309-2321
Stevenson C. E., Assaad A., Chandra G., Le T. B., Greive S. J., Bibb M. J., Lawson D. M. (2013)
Investigation of DNA sequence recognition by a streptomycete MarR family transcriptional regulator through surface plasmon resonance and X-ray crystallography.
Nucleic Acids Research 41 (14) 7009-7022
Uguru G. C., Mondhe M., Goh S., Hesketh A., Bibb M. J., Good L., Stach J. E. (2013)
Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2).
PLoS ONE 8 (6) e67509
Gomez-Escribano J. P., Bibb M. (2012)
Streptomyces coelicolor as an Expression Host for Heterologous Gene Clusters
Methods in Enzymology 517 279300
Gomez-Escribano J. P., Song L., Bibb M. J., Challis G. L. (2012)
Posttranslational β-methylation and macrolactamidination in the biosynthesis of the bottromycin complex of ribosomal peptide antibiotics.
Chemical Science 3 (12) 3522-3525
Gomez-Escribano J. P., Song L., Fox D. J., Yeo V., Bibb M. J., Challis G. L. (2012)
Structure and biosynthesis of the unusual polyketide alkaloid coelimycin P1, a metabolic product of the cpk gene cluster of Streptomyces coelicolor M145.
Chemical Science 3 (9) 2716-2720
Wyszynski F. J., Lee S. S., Yabe T., Wang H., Gomez-Escribano J. P., Bibb M. J., Lee S. J., Davies G. J., Davis B. G. (2012)
Biosynthesis of the tunicamycin antibiotics proceeds via unique exo-glycal intermediates.
Nature Chemistry 4 (7) 539-46