Explore chapters and articles related to this topic
Biosynthesis of Natural Products
Published in Ahindra Nag, Greener Synthesis of Organic Compounds, Drugs and Natural Products, 2022
Athar Ata, Samina Naz, Kenneth Friesen
Buxus alkaloids are assumed to be derived from cycloartenol-type terpenoids (72). These compounds are produced by the cyclization of squalene (67). The biosynthesis of precursor 67 starts with acetyl CoA (58) which on reaction with another molecule of acetyl CoA produces 3-hydroxy-3-methyl glutaryl SCoA (60). Compound 60 undergoes a series of reactions as outlined in Figure 16.11 to give isopentenyl pyrophosphate (62) which is isomerized to produce dimethylallyl pyrophosphate (63). A nucleophilic attack of 62 on 63 yields geranyl pyrophosphate (64). The addition of another unit of 62 to 64 produces farnesyl pyrophosphate (FPP) (65). The coupling of two FPP units in a head-to-head manner synthesizes intermediate (66) which on rearrangement affords squalene (67) (Figure 16.11).
Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
In another study, the first steps in taxol biosynthesis (Fig. 17.6) were engineered in E. coli. A multivariate modular approach was used to optimize the isoprenoid pathway taking into account the enzymes that constitute the limiting steps and modulating their expression. The pathway was divided into two modules, the first one (methylerythritol-phosphate (MEP) pathway) producing the two building blocks, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). In the second module, co-expression of geranylgeranyl pyrophosphate (GGPP) and taxadiene synthase led to the production of 1 g/L of taxadiene in fed-batch bioreactor fermentations. Moreover, the cytochrome P450 acting as taxadiene-5α-hydroxylase (Jennewein et al., 2004) was fused with its redox partner cytochrome P450 reductase (CPR) to create a self-sufficient protein leading to the production of the taxol precursor taxadien-5α-ol at a concentration of approximately 60 mg/L (Ajikumar et al., 2010). First steps of taxol biosynthesis that were successfully reached through biocatalytic approaches.
High yield production of lipid and carotenoids in a newly isolated Rhodotorula mucilaginosa by adapting process optimization approach
Published in Biofuels, 2023
Ravi Gedela, Ashish Prabhu, Venkata Dasu Veeranki, Pakshirajan Kannan
In oleaginous yeast, the hydrophilic substrate is consumed via the de novo pathway, and the lipid accumulation proceeds with the depletion of nitrogen compound, which in turns activate AMP deaminase. This activity leads toa series of cascade reactions, which disturbs the TCA cycle in mitochondria and splits the ATP-citrate lyase and acetyl-CoA and oxaloacetate. Further, the acetyl CoA is carboxylated in to malonyl CoA which is the first step of lipid synthesis, and then followed a by series of enzymatic reactions catalyzed by a complex of fatty acid synthases, which ultimately leads to the synthesis of triacyl glycerol. Further in yeast such as Rhodoturula sp that is capable of synthesizing carotenoids, which initiates by the conversion of acetyl CoA to 3 hydroxyl-3 methylglutaryl-CoA catalyzed by 3 hydroxyl-3 methylglutaryl-CoA synthase. Consequently, the HMG- CoA is reduced to mevalonic acid by HMG-CoA reductase and the cascade of reaction takes place for the production of isopentenyl diphosphate (IPP), which is further subjected to an isomerization reaction to form dimethylallyl pyrophosphate (DMAPP), and the addition of 3 molecules of IPP to DMAPP results in geranylgeranyl pyrophosphate (GGPP). The GGPP undergoes a condensation reaction catalyzed by phytoene synthase to form phytoene and finally converted to β-carotene [18]. The biochemical pathway for the formation of lipids and carotenoids in Rhodotorula sp is depicted in Figure S1 (Supplementary Material).