Geosmin synthase

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Geosmin synthase
Geosminsynthase2.png
Predicted streptomyces is a mycelial forming Actinomycete which lives in soil,they impart 'earthy odor' to soil after rain which is due to the presence of gemstones.- This point was given by s.lokeshwar 007 structure of Geosmin Synthae from I-TASSER prediction [1] [2] [3]
Identifiers
EC no. 4.1.99.16
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
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PMC articles
PubMed articles
NCBI proteins
Germacradienol synthase
Identifiers
Organism Streptomyces avermitilis
SymbolgeoA
Entrez 1210359
RefSeq (mRNA) BA000030.3
RefSeq (Prot) BAC69874.1
UniProt Q82L49
Other data
EC number 4.1.99.16
Chromosome genome: 2.64 - 2.64 Mb
Search for
Structures Swiss-model
Domains InterPro
Terpene synthase family, metal binding domain
Identifiers
SymbolTerpene_synth_C
Pfam PF03936
InterPro IPR005630
SCOP2 5eau / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Geosmin synthase or germacradienol-geosmin synthase designates a class of bifunctional enzymes (EC 4.1.99.16) that catalyze the conversion of farnesyl diphosphate (FPP) to geosmin, a volatile organic compound known for its earthy smell. [4] [5] The N-terminal half of the protein catalyzes the conversion of farnesyl diphosphate to germacradienol and germacrene D, followed by the C-terminal-mediated conversion of germacradienol to geosmin. [5] The conversion of FPP to geosmin was previously thought to involve multiple enzymes in a biosynthetic pathway. [6]

Contents

Species distribution

Geosmin is found in a wide variety of microbes such as cyanobacteria and actinobacteria. [7] [8] Geosmin has also been found in myxobacteria, fungi, arthropods, and plants such as beets. [9] Based on studies performed on a geosmin synthase (encoded by SCO6073) in Streptomyces coelicor and the high sequence similarity between this and other known or putative geosmin synthases (45-78% identity), it has been hypothesized that all geosmin synthases function in the same manner. [5] [10] Screening of available bacterial genomic data has resulted in the prediction of at least 55 putative geosmin synthases in this domain of prokaryotic organisms. [9]

Function and mechanism

Prediction of C-terminal domain of Geosmin synthase using I-TASSER Cterminalgeosmin.png
Prediction of C-terminal domain of Geosmin synthase using I-TASSER
Prediction of N-terminal domain of Geosmin synthase using I-TASSER Nterminalgeosmin.png
Prediction of N-terminal domain of Geosmin synthase using I-TASSER

Two distinct active sites

Geosmin synthase is approximately 726 amino acids in length and has two distinctive active sites on the N-terminal and C-terminal halves, respectively (in S. coelicor the N-terminal domain consists of amino acids 1-319 while the C-terminal domain exists from 374-726), both of which resembling the sesquiterpene synthase pentalenene synthase. [5] [11] Both the N- and C-terminal halves of the synthase contain aspartate-rich domains (DDHFLE and DDYYP, respectively) and the NSE amino acid motif (NDLFSYQRE and NDVFSYQKE, respectively), which bind trinuclear magnesium. [5] [12] Magnesium is a necessary cofactor, without which the synthase displays a complete lack of catalytic activity. [5]

In experiments where FPP was incubated with recombinant geosmin synthase, increasing the concentration of the synthase or increasing the incubation time resulted in an absolute and relative increase of geosmin compared to the intermediate germacradienol; this shows that geosmin synthase does not act exclusively on a series of enzyme-bound intermediates. Instead, germacradienol is released from the N-terminal domain and then rebinds to the C-terminal domain for final conversion to geosmin. [5]

Targeted mutagenesis of the N-terminal magnesium binding sites resulted in an enzyme incapable of converting FPP to germacradienol and germacrene D. [5] Targeted mutagenesis of the C-terminal magnesium-binding sites resulted in an enzyme incapable of catalyzing the second half of the reaction from germacradienol to geosmin, but still capable of converting FPP to germacradienol and germacrene D. [5] Truncated mutants of only the N-terminal or C-terminal halves of the geosmin synthase are also capable of catalyzing their respective reactions, providing further evidence that the N- and C-terminal halves of geosmin synthase are in essence two distinct and independent enzymes. [5]

N terminal repeat

The N-terminal half of geosmin synthase contains a second NSE magnesium-binding motif, approximately 38 residues downstream of the first. [5] Targeted mutagenesis of this repeated NSE motif does not significantly alter the catalytic activity of the synthase, suggesting that it does not serve any functional role. [5] This repeated downstream motif is well-conserved in other known or putative geosmin synthases, suggesting that it either has a role that has not yet been discovered or may be a remnant of evolutionary development. [5]

Proposed mechanism

The first step in the mechanism is for FPP's carbon-carbon double bond farthest from the diphosphate group to attack the carbon adjacent to the diphosphate, forming a cyclic carbocation with the loss of the diphosphate group. [5] [13] A 1,3 hydride shift moves the carbocation closer to the nearest carbon-carbon double bond; the loss of a proton forms a new carbon-carbon double bond and allows the carbon-carbon double bond adjacent to the carbocation to quench this charged group, forming the byproduct germacrene D. [5] [13] Alternatively, the carbocation produced in the first step can immediately lose a proton to form the intermediate isolepidozene, which is subsequently attacked by water to form germacradienol. [5] [13] Further processing of germacradienol involves a proton-initiated cyclization and a novel retro-Prins-type fragmentation producing the intermediate octalin and byproduct acetone. Finally, protonation, a 1,2 hydride shift, and quenching by water convert octalin to geosmin. [5] [10] [14]

Industrial importance

Geosmin has a very low detection threshold in humans of ~10-100 parts per trillion. [15] Geosmin produced by various microbes can contaminate water supplies, degrading consumer confidence and decreasing water utility performance. [7] [16] One action taken to treat geosmin contaminated water supplies is the addition of copper sulfate, which is controversial due to possible environmental effects. [17]

Studies attempting to link the expression of geosmin synthase to various environmental conditions (e.g., light and temperature) have shown synthase production to be correlated with cell growth but not significantly affected by diurnal cycles. [16] [18] Geosmin production is also correlated to the availability of substrate, as demonstrated by the deletion of pathways competing for precursors to FPP, which led to an increase in geosmin production. [18] The growing body of knowledge on geosmin synthase and its conserved and functionally important components have led to the development of a DNA PCR screen that may allow for better detection of geosmin synthase containing microorganisms, potentially allowing for better control of geosmin production and contamination in water supplies. [17]

Related Research Articles

<span class="mw-page-title-main">Geosmin</span> Chemical compound responsible for the characteristic odour of earth

Geosmin ( jee-OZ-min) is an irregular sesquiterpenoid, produced from the universal sesquiterpene precursor farnesyl pyrophosphate (also known as farnesyl diphosphate), in a two-step Mg2+-dependent reaction. Geosmin, along with the irregular monoterpene 2-methylisoborneol, together account for the majority of biologically-caused taste and odor outbreaks in drinking water worldwide. Geosmin has a distinct earthy or musty odor, which most people can easily smell. The geosmin odor detection threshold in humans is very low, ranging from 0.006 to 0.01 micrograms per liter in water. Geosmin is also responsible for the earthy taste of beetroots and a contributor to the strong scent (petrichor) that occurs in the air when rain falls after a spell of dry weather or when soil is disturbed.

<span class="mw-page-title-main">Zingiberene</span> Chemical compound

Zingiberene is a monocyclic sesquiterpene that is the predominant constituent of the oil of ginger, from which it gets its name. It can contribute up to 30% of the essential oils in ginger rhizomes. This is the compound that gives ginger its distinct flavoring.

Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ, as well as dehydrodolichol diphosphate.

The enzyme (+)-δ-cadinene synthase catalyzes the chemical reaction

<span class="mw-page-title-main">Farnesyl-diphosphate farnesyltransferase</span> Class of enzymes

Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step reaction in which two identical molecules of farnesyl pyrophosphate (FPP) are converted into squalene, with the consumption of NADPH. Catalysis by SQS is the first committed step in sterol synthesis, since the squalene produced is converted exclusively into various sterols, such as cholesterol, via a complex, multi-step pathway. SQS belongs to squalene/phytoene synthase family of proteins.

<span class="mw-page-title-main">Bornyl diphosphate synthase</span>

In enzymology, bornyl diphosphate synthase (BPPS) (EC 5.5.1.8) is an enzyme that catalyzes the chemical reaction

The enzyme amorpha-4,11-diene synthase (ADS) catalyzes the chemical reaction

The enzyme aristolochene synthase catalyzes the chemical reaction

The enzyme germacrene-A synthase (EC 4.2.3.23) catalyzes the chemical reaction

The enzyme pentalenene synthase catalyzes the chemical reaction

In enzymology, a geranyltranstransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Absinthin</span> Chemical compound

Absinthin is a naturally produced triterpene lactone from the plant Artemisia absinthium (Wormwood). It constitutes one of the most bitter chemical agents responsible for absinthe's distinct taste. The compound shows biological activity and has shown promise as an anti-inflammatory agent, and should not be confused with thujone, a neurotoxin also found in Artemisia absinthium.

<span class="mw-page-title-main">Juvabione</span> Chemical compound

Juvabione, historically known as the paper factor, is the methyl ester of todomatuic acid. Both are sesquiterpenes (C15) found in the wood of true firs of the genus Abies. They occur naturally as part of a mixture of sesquiterpenes based upon the bisabolane scaffold. Sesquiterpenes of this family are known as insect juvenile hormone analogues (IJHA) because of their ability to mimic juvenile activity in order to stifle insect reproduction and growth. These compounds play important roles in conifers as the second line of defense against insect induced trauma and fungal pathogens.

<span class="mw-page-title-main">Costunolide</span> Chemical compound

(+)-Costunolide is a naturally occurring sesquiterpene lactone, first isolated in Saussurea costus roots in 1960. It is also found in lettuce.

Germacradienol synthase (EC 4.2.3.22, germacradienol/germacrene-D synthase, 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase [(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol-forming]) is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase ((1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol-forming). This enzyme catalyses the following chemical reaction

epi-Isozizaene synthase is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase ( -epi-isozizaene-forming). This enzyme catalyses the following chemical reaction

5-Epiaristolochene synthase is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase ( -5-epiaristolochene-forming). This enzyme catalyses the following chemical reaction

Valencene synthase is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase (valencene-forming). It is a terpene cyclase enzyme responsible for the biosynthesis of valencene, a sesquiterpene, using farnesyl pyrophosphate as its substrate. The first such enzyme was isolated using orange cDNA. This enzyme catalyses the following chemical reaction

(–)-Germacrene D synthase is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase ( -germacrene-D-forming). This enzyme catalyses the following chemical reaction

7-epi-α-Selinene synthase is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase (7-epi-α-selinene-forming). This enzyme catalyses the following chemical reaction

References

  1. 1 2 3 Zhang Y (January 2008). "I-TASSER server for protein 3D structure prediction". BMC Bioinformatics. 9 (40): 40. doi: 10.1186/1471-2105-9-40 . PMC   2245901 . PMID   18215316.
  2. 1 2 3 Roy A, Kucukural A, Zhang Y (April 2010). "I-TASSER: a unified platform for automated protein structure and function prediction". Nature Protocols. 5 (4): 725–38. doi:10.1038/nprot.2010.5. PMC   2849174 . PMID   20360767.
  3. 1 2 3 The PyMOL Molecular Graphics System, Version 1.5.0.4 Schrödinger, LLC.
  4. ↑ Q9X839 (CYC2_STRCO) Reviewed, UniProtKB/Swiss-Prot, UniProt, November 28, 2012, retrieved February 17, 2013
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Jiang J, He X, Cane DE (November 2007). "Biosynthesis of the earthy odorant geosmin by a bifunctional Streptomyces coelicolor enzyme". Nature Chemical Biology. 3 (11): 711–5. doi:10.1038/nchembio.2007.29. PMC   3013058 . PMID   17873868.
  6. ↑ Daum M, Herrmann S, Wilkinson B, Bechthold A (April 2009). "Genes and enzymes involved in bacterial isoprenoid biosynthesis". Current Opinion in Chemical Biology. 13 (2): 180–8. doi:10.1016/j.cbpa.2009.02.029. PMID   19318289.
  7. 1 2 Agger SA, Lopez-Gallego F, Hoye TR, Schmidt-Dannert C (September 2008). "Identification of sesquiterpene synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. strain PCC 7120". Journal of Bacteriology. 190 (18): 6084–96. doi:10.1128/jb.00759-08. PMC   2546793 . PMID   18658271.
  8. ↑ Gerber NN, Lechevalier HA (November 1965). "Geosmin, an earthly-smelling substance isolated from actinomycetes". Applied Microbiology. 13 (6): 935–8. doi:10.1128/am.13.6.935-938.1965. PMC   1058374 . PMID   5866039.
  9. 1 2 Citron CA, Gleitzmann J, Laurenzano G, Pukall R, Dickschat JS (January 2012). "Terpenoids are widespread in actinomycetes: a correlation of secondary metabolism and genome data". ChemBioChem. 13 (2): 202–14. doi:10.1002/cbic.201100641. PMID   22213220. S2CID   20073111.
  10. 1 2 Jiang J, Cane DE (January 2008). "Geosmin biosynthesis. Mechanism of the fragmentation-rearrangement in the conversion of germacradienol to geosmin". Journal of the American Chemical Society. 130 (2): 428–9. doi:10.1021/ja077792i. PMC   2533842 . PMID   18095692.
  11. ↑ Cane DE, Watt RM (February 2003). "Expression and mechanistic analysis of a germacradienol synthase from Streptomyces coelicolor implicated in geosmin biosynthesis". Proceedings of the National Academy of Sciences of the United States of America. 100 (4): 1547–51. doi: 10.1073/pnas.0337625100 . PMC   149869 . PMID   12556563.
  12. ↑ Degenhardt J, Köllner TG, Gershenzon J (October 2009). "Monoterpene and sesquiterpene synthases and the origin of terpene skeletal diversity in plants". Phytochemistry. 70 (15–16): 1621–37. doi:10.1016/j.phytochem.2009.07.030. PMID   19793600.
  13. 1 2 3 He X, Cane DE (March 2004). "Mechanism and stereochemistry of the germacradienol/germacrene D synthase of Streptomyces coelicolor A3(2)". Journal of the American Chemical Society. 126 (9): 2678–9. doi:10.1021/ja039929k. PMID   14995166.
  14. ↑ Jiang J, He X, Cane DE (June 2006). "Geosmin biosynthesis. Streptomyces coelicolor germacradienol/germacrene D synthase converts farnesyl diphosphate to geosmin". Journal of the American Chemical Society. 128 (25): 8128–9. doi:10.1021/ja062669x. PMID   16787064.
  15. ↑ Cane DE, He X, Kobayashi S, Omura S, Ikeda H (August 2006). "Geosmin biosynthesis in Streptomyces avermitilis. Molecular cloning, expression, and mechanistic study of the germacradienol/geosmin synthase". The Journal of Antibiotics. 59 (8): 471–9. doi: 10.1038/ja.2006.66 . PMID   17080683.
  16. 1 2 Giglio S, Saint CP, Monis PT (December 2011). "Expression of the Geosmin Synthase Gene in the Cyanobacterium Anabaena Circinalis AWQC318(1)". Journal of Phycology. 47 (6): 1338–43. doi:10.1111/j.1529-8817.2011.01061.x. PMID   27020357. S2CID   205697117.
  17. 1 2 Giglio S, Jiang J, Saint CP, Cane DE, Monis PT (November 2008). "Isolation and characterization of the gene associated with geosmin production in cyanobacteria". Environmental Science & Technology. 42 (21): 8027–32. doi:10.1021/es801465w. PMC   2746953 . PMID   19031897.
  18. 1 2 Singh B, Oh TJ, Sohng JK (October 2009). "Exploration of geosmin synthase from Streptomyces peucetius ATCC 27952 by deletion of doxorubicin biosynthetic gene cluster". Journal of Industrial Microbiology & Biotechnology. 36 (10): 1257–65. doi: 10.1007/s10295-009-0605-0 . PMID   19557446. S2CID   22285729.
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