## 3 Utilization of Precursor Compounds from Primary Metabolism in Secondary Metabolism
### Supply of Key Precursors Carbon, Nitrogen, Phosphate and Sulfur for Secondary Metabolism
#### 3.2.1. Supply of Carbon for Secondary Metabolism  
Carbon can be introduced into diverse compounds as a part of amino acid building blocks or via sugars and their derivatives. The amino acid metabolism building blocks are supplied for the synthesis of secondary metabolites, for example, non-ribosomally synthesized peptides (such as glycoptides), and ribosomally synthesized and post-translationally modified peptides (RIPPs). From the special synthesis of non-proteinogenic amino acids, which are derived from the precursor synthesis of other amino acids, e.g., via the shikimate pathway, building blocks can also be supplied for the production of secondary metabolites, e.g., glycopeptides. The use of these building blocks in the special synthesis of proteinogenic amino acids was also reported, e.g., pipecolic acid synthesis from lysine [93].  
Amino acids synthesized through Acyl-CoA are the building blocks for peptides, proteins and lipids, and can form precursors for diverse metabolites, e.g., leucine, isoleucine, lysine, and valine serve as precursors for industrially important polyketides [102]. Acyl-CoA can be supplied from glycolysis or fatty acid degradation as building blocks for polyketide synthases (PKSs), such as malonyl-CoA. Lipid components for secondary metabolism can be supplied by PKSs. Once absorbed into the cell, amino acids are predominantly metabolized as precursors and are not directly incorporated into antibiotics. It has been shown that the effect of the addition of amino acids to secondary metabolite production is predominantly based on its function as a carbon source [103].  
Sugars were described to be building blocks for the production of diverse antibiotics. Metabolic pathways like glycolysis and the pentose phosphate pathway provide sugar phosphates that can be used as building blocks in secondary metabolite biosynthesis [104]. In addition, many secondary metabolite processes take advantage of products or intermediates of cell envelope biosynthesis. Such sugars can either be directly used or they are further specifically modified in the course of secondary metabolite biosynthesis. They can build the backbone structure of antibiotics (e.g., in aminoglycos). Furthermore, such sugars are used to decorate polyketides and peptides.  
The amino acid biosynthetic pathways that involve feedback inhibition are the synthesis pathways for arginine, lysine and aromatic amino acids. Lysine is a building block for many secondary metabolites. It is frequently used as a media additive in industry. The gene encoding the lysine cyclodeaminase is localized in associated biosynthetic gene clusters, like in the cluster of the streptogram pristinamycin (_pipA_) [105], the lipopeptide antibiotic friulinicin (_pip_) [106], tacrolimus (_fkDL_) [93] and rapamycin [107]. It has been demonstrated for all producers that the overexpression of lysine cyclodeaminase genes leads to an increase in titers of target secondary metabolites. Increased lysine availability has been demonstrated to positively impact and lead to increased secondary metabolite production from cephalospor biosynthesis in _S. clavuligerus_[108] and tacrolimus (FK-506) biosynthesis in _S. tsukubaensis_[93].