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.
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
Gomez-Escribano J. P., Bibb M. (2012)
Streptomyces coelicolor as an Expression Host for Heterologous Gene Clusters
Methods in Enzymology 517 279–300
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
Claesen J., Bibb M. J. (2011)
Biosynthesis and regulation of Grisemycin, a new member of the linaridin family of ribosomally synthesized peptides produced by Streptomyces griseus IFO 13350.
Journal of Bacteriology 193 (10) 2510-2516
Foulston L., Bibb M. (2011)
Feed-forward regulation of microbisporicin biosynthesis in Microbispora corallina.
Journal of Bacteriology 193 (12) 3064-3071
Gomez-Escribano J. P., Bibb M. J. (2011)
Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters
Microbial Biotechnology 4 (2) 207-215
Gottardi E. M., Krawczyk J. M., von Suchodoletz H., Schadt S., Mühlenweg A., Uguru G. C., Pelzer S., Fiedler H. P., Bibb M. J., Stach J. E., Süssmuth R. D. (2011)
Abyssomicin biosynthesis: formation of an unusual polyketide, antibiotic-feeding studies and genetic analysis.
ChemBioChem 12 (9) 1401-1410
Hesketh A., Hill C., Mokhtar J., Novotna G., Tran N., Bibb M., Hong H. J. (2011)
Genome-wide dynamics of a bacterial response to antibiotics that target the cell envelope
BMC Genomics 12 (1) 226
Murakami T., Burian J., Yanai K., Bibb M. J., Thompson C. J. (2011)
A system for the targeted amplification of bacterial gene clusters multiplies antibiotic yield in Streptomyces coelicolor.
Proceedings of the National Academy of Sciences of the United States of America 108 (38) 16020-16025
Murakami T., Sumida N., Bibb M., Yanai K. (2011)
ZouA, a putative relaxase, is essential for DNA amplification in Streptomyces kanamyceticus.
Journal of Bacteriology 193 (8) 1815-1822
Pullan S. T., Chandra G., Bibb M. J., Merrick M. (2011)
Genome-wide analysis of the role of GlnR in Streptomyces venezuelae provides new insights into global nitrogen regulation in actinomycetes
BMC Genomics 12 175
Roh H., Uguru G. C., Ko H. J., Kim S., Kim B. Y., Goodfellow M., Bull A. T., Kim K. H., Bibb M. J., Choi I. G., Stach J. E. (2011)
Genome sequence of the Abyssomicin and Proximicin-producing marine actinomycete Verrucosispora maris AB-18-032.
Journal of Bacteriology 193 (13) 3391-3392
Seipke R. F., Crossman L., Drou N., Heavens D., Bibb M. J., Caccamo M., Hutchings M. I. (2011)
Draft genome sequence of Streptomyces strain S4, a symbiont of the leaf-cutting ant Acromyrmex octospinosus
Journal of Bacteriology 193 (16) 4270-4271