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Extra info for Advances in Biochemical Engineering Biotechnology Metabolic Engineering
60. 61. 62. 63. 64. 65. 66. 67. 68. 69. edu Polyketide natural products are a rich source of bioactive substances that have found considerable use in human health and agriculture. Their complex structures require that they be produced via fermentation processes. This review describes the strategies and challenges used to develop practical fermentation strains and processes for polyketide production. Classical strain improvement procedures, process development methods, and metabolic engineering approaches are described.
2 Media Development The objective in many media development programs is to improve the volumetric productivity (grams per liter per day) by evaluating the carbon, nitrogen, vitamin/growth factor, and inorganic nutrition requirements of the culture [4, 7, 18]. The solution to this aim will likely entail increasing the cell density while at the same time providing an environment conducive to maximizing the specific productivity (1/X (dP/dt), Qp). Although there exist a number of reports on improving secondary metabolite productivity [4, 7, 19, 20], media development remains an iterative process.
Unfortunately, the use of high copy expression plasmids to increase PKS gene copy number has not been possible, which may either be due to plasmid instability or toxicity effects. 42 R. McDaniel et al. A final consideration for overexpression of PKSs is the post-translational phosphopantethienylation required to generate biosynthetically active PKS enzymes. This modification is performed by an enzyme called a holo-ACP synthase  (Fig. 3). Co-expression of a holo-ACP synthase with appropriate specificity is required for expression of PKSs in E.
Advances in Biochemical Engineering Biotechnology Metabolic Engineering by Georg Gübitz, Alexander Bauer, Guenther Bochmann, Andreas Gronauer, Stefan Weiss