Classification of Natural Products Fatty acid-derived substances and polyketides More than 10,000 known Biosynthesized from simple acyl precursors such as acetyl CoA,propionyl CoA,and methylmalonyl CoA Natural products derived from fatty acids,such as prostaglandin E1,generally have most of the oxygen atoms removed Polyketides,such as the antibiotic erythromycin,often have many oxygen substituents remaining
Fatty acid-derived substances and polyketides ▪ More than 10,000 known ▪ Biosynthesized from simple acyl precursors such as acetyl CoA, propionyl CoA, and methylmalonyl CoA ▪ Natural products derived from fatty acids, such as prostaglandin E1 , generally have most of the oxygen atoms removed ▪ Polyketides, such as the antibiotic erythromycin, often have many oxygen substituents remaining Classification of Natural Products
Classification of Natural Products Nonribosomal polypeptides Peptidelike compounds Biosynthesized from amino acids by a multifunctional enzyme complex without direct RNA transcription,such as penicillins Enzyme cofactors Coenzymes such as pyridoxal phosphate(PLP)
Nonribosomal polypeptides ▪ Peptidelike compounds ▪ Biosynthesized from amino acids by a multifunctional enzyme complex without direct RNA transcription, such as penicillins Enzyme cofactors ▪ Coenzymes such as pyridoxal phosphate (PLP) Classification of Natural Products
25-2 Biosynthesis of Pyridoxal Phosphate 0 -0 00 Figure 25.1 一OH H 一OH C=0 一OH 0 一OH H -OH 3 H -OH Pathway for pyridoxal 5'- CH20P032 CH20P032 CH20P032 CH20P032 phosphate biosynthesis D-Erythronate 3-Hydroxy-4-phospho- 4-Phospho- 4-phosphate hydroxy-2-ketobutyrate hydroxythreonine CH3 CH3 Pyruvate =0 co. =0 HO- H 0P033 OH 0 H CH20P032 1-Amino-3-hydroxy- D-Glyceraldehyde acetone 3-phosphate 3-phosphate -OH 1-Deoxyxylulose CH2OPO32- 5-phosphate 6 CH20P032 CH2OH Pyridoxine 5'-phosphate OH CH3 0 CH2OPO32 CHO Pyridoxal 5'-phosphate(PLP) OH
Figure 25.1 Pathway for pyridoxal 5′- phosphate biosynthesis 25-2Biosynthesis of Pyridoxal Phosphate
Biosynthesis of Pyridoxal Phosphate STEPS 1-2 OF FIGURE 25.1:OXIDATION Biosynthesis of pyridoxal phosphate begins with oxidation of aldehyde group in D-erythrose 4-phosphate to give D- erythronate 4-phosphate Requires NAD+as cofactor Cysteine-SH group in enzyme adds to aldehyde carbonyl group of D-erythrose 4-phosphate to give intermediate hemithioacetal Hemithioacetal is oxidized by NAD+to a thioester Hydrolysis of thioester yields erythronate 4-phosphate
STEPS 1-2 OF FIGURE 25.1: OXIDATION Biosynthesis of pyridoxal phosphate begins with oxidation of aldehyde group in D-erythrose 4-phosphate to give Derythronate 4-phosphate ▪ Requires NAD+ as cofactor ▪ Cysteine –SH group in enzyme adds to aldehyde carbonyl group of D-erythrose 4-phosphate to give intermediate hemithioacetal ▪ Hemithioacetal is oxidized by NAD+ to a thioester ▪ Hydrolysis of thioester yields erythronate 4-phosphate Biosynthesis of Pyridoxal Phosphate
Biosynthesis of Pyridoxal Phosphate Oxidation of thioester-OH group at C2 by NAD+gives 3- hydroxy-4-phosphohydroxy-2-ketobutyrate NAD+ Enz Enz CONH2 -H NADH/H+ H20 En2SH OH OH H OH -OH H -OH OH CH20P032 CH20P032 CH20P032 D-Erythrose Hemithioacetal Thioester 4-phosphate 0c0 NAD+ NADH/H+ H OH C=0 H -OH H -OH CH20P032 CH2OPO32- D-Erythronate 3-Hydroxy-4-phospho- 4-phosphate hydroxy-2-ketobutyrate
▪ Oxidation of thioester –OH group at C2 by NAD+ gives 3- hydroxy-4-phosphohydroxy-2-ketobutyrate Biosynthesis of Pyridoxal Phosphate