Wednesday, November 11, 2009 - 11:00 AM
S36
Streptomycete hosts for the heterologous expression of secondary metabolite biosynthetic gene clusters. Richard H. Baltz
R. H. Baltz, Cubist Pharmaceuticals, Lexington, MA 2421
DNA sequence analysis of several large actinomycete genomes has revealed that most strains encode multiple secondary metabolite biosynthetic pathways, only a fraction of which are normally expressed during typical fermentations. Recent advances in DNA sequencing technology have made it economical to sequence multiple actinomycete genomes as an approach to identify potential novel secondary metabolites. One approach to express otherwise cryptic pathways is to clone them in cosmid or bacterial artificial chromosome (BAC) vectors, and insert them into heterologous hosts with known metabolite profiles, then search for novel mass ions and pharmacological activities. This approach can be augmented by transcriptional profiling and by inserting strong promoters in front of key nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) transcriptional units. There are several common laboratory strains that have been used extensively to express complete secondary metabolite pathways. There are also industrial and experimental strains not commonly used that may have important features to facilitate the expression of cryptic pathways. In this talk, I summarize the advantages and disadvantages of several different streptomycete hosts, including several not commonly used in past studies.
See more of Advances, practices and improvements in fermentation of antibiotics and secondary metabolites
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See more of RAFT VIII (November 8 - 11, 2009)
See more of Invited Oral Papers
See more of RAFT VIII (November 8 - 11, 2009)