Isoprenoids in bacteria

From the many enzymes that are known to make and break C-C bonds, we first chose the two transferases, transketolase (TKT) and transaldolase (TAL), both from the Gram-negative bacterium Escherichia coli. While project B21 evolved, we learned that this microorganism holds other and so far unknown enzymes which are of interest for asymmetric syntheses. One transketolase-like enzyme, 1-deoxy-D-xylulose 5-phosphate synthase (DXS), turned out to be the first enzyme of a novel biosynthetic pathway leading to isoprenoids in bacteria, algae, and plants. The other, fructose 6-phosphate aldolase (ESA) - while similar to transaldolase - allows the direct use of the inexpensive dihydroxyacetone in aldol condensations. 

It has been established that DXS catalyzes the first step in a novel biosynthetic pathway leading to isoprenoids in bacteria, algae, plant chloroplasts, and in the malaria parasite, Plasmodium falciparum. DXS is therefore a novel target for antibiotics, herbicides, or anti-malarials. Our work has contributed to an understanding of the novel biosynthetic pathway and could further open new perspectives on how to inhibit the pathway in pathogenic bacteria, protists, or weeds. 

Vickers, C., Bongers, M., Bydder, S., Chrysanthopoulos, P. et al. (2015) Protocols for the Production and Analysis of Isoprenoids in Bacteria and Yeast. In Hydrocarbon and Lipid Microbiology Protocols (eds T.J. McGenity et al.), Springer, Verlag Berlin Heidelber, ppi 23-52. 

Rohmer, M., The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants, Nat. Prod. Rep., 16, 565, 1999. 

ROHMER, M., KNANI, M., SIMONIN, P., SUTTER, B., SAHM, H., Isoprenoid biosynthesis in bacteria a novel pathway for the early steps leading to isopentenyl diphosphate, Biochem. J., 1993,295, 517-524. 

Collins, M.D. and Jones, D. (1 981) Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication. Microbiological Reviews 45, 31 6-354. 

Horbach, S., Sahm, H. and Welle, R. (1993) Isoprenoid biosynthesis in bacteria two different pathways FEMS Microb. Lett., Ill, 135 0. 

In bacteria, the thiazole moiety (42) of thiamine is derived from 1-deoxy-D-xylulose 5-phosphate (43) that can also serve as a precursor for pyridoxal in many eubacteria (Fig. 5) and for isoprenoids via the nonmevalonate pathway (cf. isoprenoid cofactors). The sulfur atom is derived from the persulfide that also serves as precursor for iron/sulfur clusters and for biotin (6) and thiooctanoate (7) (Fig. 1). C2 and N3 of the thiazole moiety of thiamine have been reported to stem from tyrosine in Escherichia coli and from glycine in Bacillus subtilis, respectively. Yeasts use ADP-ribulose (44) derived from NAD as precursor (24). 

The MEP pathway is the only pathway involved in the biosynthesis of essential isoprenoids in pathogenic bacteria and in parasites, and it is absent in animals and in humans. Therefore, any enzyme of this pathway is a potential target for a novel type of antimicrobial drugs (16, 17). This concept has been validated by the mode of action of fosmidomycin, a natural antibiotic that inhibits the second step of the MEP pathway catalyzed by the deoxyxylulose phosphate reducto-isomerase (DXR). 

Isoprenoid biosynthesis in bacteria a novel pathway for the early steps leading to isopentenyl diphosphate. Biochem. J. 295, 517-524. 

Summons R. E. and Powell T. G. (1987) Identification of aryl isoprenoids in source rocks and crude oils biological markers for the green sulphur bacteria. Geochim. Cosmochim. Acta 51, 557-566. 

Biosynthesis. An alternative pathway has been proposed for the early stages of the biosynthesis of the isoprenoid side-chain of ubiquinone in bacteria, via acetolactate rather than acetoacetate.285 3,4-Dihydroxy-5-hexaprenylbenzoic acid (248)286 and... 

Rodriguez-Concepcion M. and A. Boronat Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics. Plant Physiol. 130(2002) 1079-1089. 

HMG-CoA reductase activity has been detected in mammals, birds, insects, reptiles, fish, higher plants, moulds, yeast and bacteria [112]. HMG-CoA reductase probably is present in any life form capable of synthesizing isoprenoids. In mammals, HMG-CoA reductase activity has been detected in many tissues (Table 3). The highest quantities are present in liver and intestine, which together provide 2/3-3/4... 

Processes affecting the carbon-isotopic compositions of isoprenoid lipids. The isoprene carbon skeleton is indicated schematically in Figure 27. The corresponding biosynthetic reactant—equivalent in its role to acetyl-CoA—is isopentenyl pyrophosphate. As shown in Figure 29, this compound can be made by two different and fully independent pathways. The mevalonic-acid pathway was until recently thought to be the only route to isoprenoids. The deoxyxylulose-phosphate, or methylerythritol-phosphate, pathway was first discovered in Bacteria by Rohmer and coworkers (Flesch and Rohmer... 

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