Successful engineering of antibiotic biosynthesis depends on the comprehensive understanding of the biology of the producing organism. We are studying two aspects of Streptomyces coelicolor A3(2), the model organism for antibiotic biosynthesis:
Mycelial growth and morphological differentiation
Regulation of antibiotic synthesis is deeply intertwined with the control of morphological differentiation. Our studies focus on the Streptomyces Spore wall Synthesizing Complex SSSC, a set of proteins involved in sporulation septation and synthesis of the spore envelope.
Fig. 1 Apical tip growth and sporulation septation visualized by BODIPY™ FL vancomycin staining
Plasmid biology and horizontal gene transfer
Streptomycetes contain a plethora of mobile genetic elements including small and larger circular plasmids, huge linear plasmids of several hundred kbp in size, and Actinomycete Integrative and Conjugative Elements (AICE). These elements direct the shaping of Streptomyces genomes and might have a particular role in the evolution and diversification of biosynthetic gene clusters. As producers of antibiotics, actinomycetes are regarded as the natural source and reservoir of antibiotic resistance genes which have been developed as part of the biosynthetic gene clusters to protect the producer from its own antibiotic. By horizontal gene transfer, the resistance determinants probably found their way into pathogenic bacteria causing major health problems.
Fig. 2 Conjugative transfer and intramycelial spreading of plasmid pLT303, visualized by fluorescence microscopy.
Spores of the donor S. lividans TK23 (pLT303) (green) and the recipient S. lividans T7–mCherry (red) were mixed and plated. After 20 h of growth at 29°C cells were imaged by fluorescence microscopy. Transconjugants appear yellow in the overlay.