A minimal nucleotide metabolism based on salvage pathways. Activated ribonucleotides and deoxyribonucleotides are obtained from free bases (A, G, and U), PRPP, ATP-dependent phosphorylating reactions, and NADH-dependent reduction. White boxes indicate the individual enzymatic activity (EC number and coding gene). Other colors are used as in Fig. 1.

A minimal metabolism. The minimal cell can obtain its more basic components from the environment: glucose, fatty acids, amino acids, adenine, guanine, uracil, and coenzyme precursors (nicotinamide, riboflavin, folate, pantothenate, and pyridoxal). Each box includes the metabolic transformations classified in major groups of pathways: glycolysis, phospholipid biosynthesis, nonoxidative pentose-phosphate pathway, nucleotide biosynthesis, synthesis of enzymatic cofactors, and synthesis of protein precursors, i.e., aminoacyl-tRNAs (aa-tRNA). Arrows with discontinuous lines represent incorporation from the environment. Single continuous arrows represent single enzymatic steps, whereas wide arrows represent several enzymatic steps (the number within the arrow indicates the number of steps). Lines with a final black point indicate the necessity of metabolites for some of the transformations inside the corresponding box. Metabolic intermediates and final pathway products are in green boxes. Metabolites acting as a source of chemical energy are in red boxes. Reducing-power cofactors are in light blue boxes. Abbreviations (besides the accepted symbols and those defined in the text): PEP, phosphoenolpyruvate; G6P, glucose-6-phosphate; Gd3P, glyceraldehyde-3-phosphate; DHAP, dihydroxyacetonephosphate; G3P, sn-glycerol-3-phosphate; CDP-DAG, CDP-diacylglycerol; SAM, S-adenosylmethionine; THF, tetrahydrofolate. Metabolic precursors of external origin are in gray boxes.

Biosynthesis of cofactors. A metabolism of essential cofactors used by the minimal cell starting with precursors (i.e., vitamins): nicotinamide, riboflavin, thiamine, pyridoxal, patothenic acid, methionine, and folic acid. Yellow boxes indicate the enzymes that need each cofactor for their correct function. Other colors and symbols are as in Fig. 1 and 2. PP, pyridoxal-phosphate.