Production of bicyclic and tricyclic triterpenes by mutated squalene-hopene cyclase

Pale-Grosdemange, Catherine; Merkofer, Thorsten; Rohmer, Michel; Poralla, Karl

doi:10.1016/s0040-4039(99)01248-4

Cited by 38 publications

(41 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, B. subtilis SqhC contains functional motifs responsible for some critical steps of cyclase activity: a domain rich in aspartic acid initiates the protonation of a polyprene precursor, and aromatic residues are present that would stabilize the first two cyclohexyl rings (5) (SI Text). In contrast to most known squalene-hopene cyclases, however, SqhC does not contain residue F601 that would enable formation of the third cyclohexyl ring from a squalene precursor (7,8). Thus, B. subtilis would be expected to produce cyclic polyprenoids, but not hopanoids.…”

Section: Biosynthesis Of Polycyclic Terpenoids By Bacillus Subtilismentioning

confidence: 98%

A polycyclic terpenoid that alleviates oxidative stress

Bosak

Losick

Pearson

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Polycyclic terpenoid lipids such as hopanes and steranes have been widely used to understand ancient biology, Earth history, and the oxygenation of the ocean-atmosphere system. Some of these lipids are believed to be produced only by aerobic organisms, whereas others actually require molecular oxygen for their biosynthesis. A persistent question remains: Did some polycyclic lipids initially evolve in response to certain environmental or metabolic stresses, including the presence of oxygen? Here, we identify tetracyclic isoprenoids in spores of the bacterium Bacillus subtilis. We call them sporulenes. They are produced by cyclization of regular polyprenes, a reaction that is more favorable chemically than the formation of terpenoids such as hopanoids and steroids from squalene. The simplicity of the reaction suggests that the B. subtilis cyclase may be analogous to evolutionarily ancient cyclases. We show that these molecules increase the resistance of spores to a reactive oxygen species, demonstrating a specific physiological role for a nonpigment bacterial lipid biomarker. Geostable derivatives of these compounds in sediments could thus be used as direct indicators of oxidative stress and aerobic environments.biomarker ͉ spores ͉ squalene-hopene cyclase ͉ lipid ͉ peroxide resistance P olycyclic terpenoids are a class of organic molecules that includes cholesterol and numerous other related lipids. Their molecular fossils, which are ubiquitous in the sedimentary rock record, are used as records of ancient bacterial and eukaryotic life. For example, the timing of the onset of oxygenic photosynthesis has been reported to be as early as 2.7 billion years ago (1) based on the detection of polycyclic terpenoids presumably derived from Cyanobacteria (2). However, recent studies have questioned this assumption and have urged caution about making taxonomic associations of specific lipid biomarkers with specific microbial groups (3, 4).Here, we take a different approach to this debate by showing definitively that some polycyclic terpenoids reflect a specific physiological function. The association of molecular fossils with physiological functions reduces the dependence of molecular fossils on specific organisms and taxonomic groups. Significantly, we demonstrate in vivo the protective role of a class of polycyclic terpenoids against a reactive oxygen species. Geostable derivatives of these compounds, called sporulenes, could become more definitive geologic markers for aerobic bacteria and environments. Future studies of the specific biological roles of other polycyclic terpenoids may greatly inform the interpretations of the past, including the oxygenation of the Earth. Biosynthesis of Polycyclic Terpenoids by Bacillus subtilisThe best-studied polycyclic terpenoids, tetracyclic sterols and pentacyclic hopanoids, are produced enzymatically from acyclic 30-carbon (C 30 ) precursors by a family of squalene and oxidosqualene cyclases (5, 6). A gene (sqhC) encoding a putative squalene cyclase enzyme (SqhC) is present in a two...

show abstract

Section: Biosynthesis Of Polycyclic Terpenoids By Bacillus Subtilismentioning

confidence: 98%

A polycyclic terpenoid that alleviates oxidative stress

Bosak

Losick

Pearson

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…15) However, X-ray information on the SHC-inhibitor complex shows that these residues are located close to the inhibitor of N, N-dimethyldodecylamine-N-oxide (LDAO), 16,17) implying that the two residues may be responsible for catalysis. Indeed, Poralla and co-workers have reported that the Tyr420Ala mutant produced three abortive cyclization products consisting of two bicycles, aand g-polypodatetraene, and one tricycle, malabaricatriene, 18,19) and that the Leu607Lys mutant gave bicyclic g-polypodatetraene. 20) However, no kinetic data were presented.…”

Section: )mentioning

confidence: 99%

Functional Analyses of Tyr420 and Leu607 of Alicyclobacillus acidocaldarius Squalene-Hopene Cyclase. Neoachillapentaene, a Novel Triterpene with the 1,5,6-Trimethylcyclohexene Moiety…

Sato

Sasahara

Yamakami

et al. 2002

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

“…This was in sharp contrast to the observations reported for the hydrocarbon fraction in Alicyclobacillus acidocaldarius. Whole cells or the puri¢ed squalene cyclase of this bacterium produced mainly diploptene (12) and diplopterol (hopan-22-ol) and only trace amounts of these unexpected hydrocarbons with shorter GC retention times than that of diploptene [9]. GC-MS analysis of the total hydrocarbon mixture showed that all these novel Z. mobilis metabolites were characterized by an m/z 410 molecular ion and were accordingly isomers of squalene and diploptene.…”

Section: Resultsmentioning

confidence: 98%

“…The GC-MS analysis of the total hydrocarbon fraction of Z. mobilis showed the presence of many triterpenes with retention times between those of squalene (1) and diploptene (12) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Structural diversity of the triterpenic hydrocarbons from the bacterium Zymomonas mobilis: the signature of defective squalene cyclization by the squalene/hopene cyclase

Douka¹

2001

FEMS Microbiology Letters

View full text Add to dashboard Cite

Twelve polycyclic triterpenic hydrocarbons (K-and Q-polypodatetraenes, dammara-20(21),24-diene, 17-isodammara-12,24-diene, eupha-7,24-diene, hop-17(21)-ene, neohop-13(18)-ene, 17-isodammara-20(21),24-diene, neohop-12-ene, fern-8-ene, diploptene and hop-21-ene) were detected in the hydrocarbon fraction from the bacterium Zymomonas mobilis. Some of them have never been reported from bacteria. These triterpenes were present in Z. mobilis in significant amounts, comparable to those of diploptene, which is usually the major triterpenic hydrocarbon in hopanoid-producing bacteria. The occurrence of such compounds confirms the lack of specificity of bacterial squalene cyclases and the possibility of alternative cyclization routes induced by the existence in the cyclization process of intermediate carbocations of sufficient lifetime. ß

show abstract

Production of bicyclic and tricyclic triterpenes by mutated squalene-hopene cyclase

Cited by 38 publications

References 11 publications

A polycyclic terpenoid that alleviates oxidative stress

A polycyclic terpenoid that alleviates oxidative stress

Functional Analyses of Tyr420 and Leu607 of Alicyclobacillus acidocaldarius Squalene-Hopene Cyclase. Neoachillapentaene, a Novel Triterpene with the 1,5,6-Trimethylcyclohexene Moiety…

Structural diversity of the triterpenic hydrocarbons from the bacterium Zymomonas mobilis: the signature of defective squalene cyclization by the squalene/hopene cyclase

Contact Info

Product

Resources

About