Advances in Biochemical Engineering Biotechnology Metabolic by Georg Gübitz, Alexander Bauer, Guenther Bochmann, Andreas

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Continued) Process Development and Metabolic Engineering 46 R. McDaniel et al. for overexpression to increase methylmalonyl-CoA availability. In this case, it becomes important to provide high levels of propionyl-CoA, which can be derived from both branched chain amino acid degradation and odd or branched chain fatty acid degradation [86]. It may also be possible to enhance levels of propionyl-CoA by supplementing the fermentation with propionate and overexpressing the corresponding CoA ligase and transport enzymes, although enzymes with these specific activities have not been identified yet.

As many secondary metabolites can be produced by a single Actinomycete host organism, regulatory proteins are generally divided into two classes – pathway specific regulators which affect only a single polyketide (or other natural product) pathway and global (or pleiotropic) regulators which affect multiple or all pathways. The signaling pathways of the latter are less understood and are often coupled to physiological differentiation such as formation of aerial hyphae and spores. Many of these regulators belong to a unique family of transcriptional activators called Streptomyces antibiotic regulatory proteins (SARPs) [69].

McDaniel et al. 85. Rodriguez E, Gramajo H (1999) Genetic and biochemical characterization of the a and b components of a propionyl-CoA carboxylase complex of Streptomyces coelicolor A3(2). Microbiol 145:3109–3119 86. Tang L, Xhang Y-X, Hutchinson CR (1994) Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide iosynthesis in Streptomyces ambofaciens and Streptomyces fradiae. J Bacteriol 176:6107–6119 87. Birch A, Leiser A, Robinson JA (1993) Cloning, sequencing, expression of the gene encoding methylmalonyl-coenzyme A mutase from Streptomyces cinnamonensis.

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