Artificial Chromosomes to Explore and to Exploit Biosynthetic Capabilities of Actinomycetes

Figure 4

Strategies adopted to improve heterologous production of daptomycin, meridamycin, and migrastatin in heterologous hosts. Under “fermentation strategies" fall feeding with biosynthetic precursors or growth in presence of specific nutrients. Host genetic manipulation indicates the inactivation of host biosynthetic pathways or mutations in genes (rpsL and rpoB) known for increasing secondary metabolite production. Genetic cluster manipulation refers to the cloning of a strong promoter upstream of foreign genes which are weakly transcribed. Details are provided in the text.