# Bacterial Semichemicals and Transkingdom Interactions with Insets and Plants
## 3 BVOC Biosynthetic Pathways and Their Intersections with Primary and Secondary Metabolism
### BVOCs and Secondary Metabolism
#### 3.2.2 Terpene and Terpenoid Metabolism in Bacteria
It has been proposed that the non-individuated MVA pathway enzymes likely evolve independently to complete the pathway, are supplementary enzymes that can be provided in _trans_ configuration by other pathways, or are moonlighting proteins with two or more functions [146; 147]. Details of the MVA pathway are illustrated in Figure 5. The first three steps, called the lower mevalonate pathway, are catalyzed, respectively, by acetoacetyl-CoA thiolase (AACT), HMG-CoA synthase (HMGS), and HMG-CoA reductase (HMGR) [148]. The result of lower pathway is the key precursor mevalonate and is then converted to mevalonate 5-phosphate by mevalonate kinase (MVK). This molecule is converted into IPP by two reactions which, in eukaryotes, involve phospho-mevalonate kinase (PMK) and mevalonate-diphosphate decarboxylase (MDC) while, in archaea, they involve a putative phospho-mevalonate decarboxylase (MPD) and a characterized isopentenyl phosphate kinase (IPK) [148]. Isomerization of IPP to DMAPP is carried out by distinct isopentenyl pyrophosphate isomerases in eukaryotes (IDI1) and archaea (IDI2) [148]. There is evidence that the MVA pathway exists and is essential in several bacteria, including staphylococci, streptococci, and enterococci, at variance with _Bacillus subtilis_ and gram-negative bacteria that possess the MEP pathway. For example, in _S. aureus_, the mevalonate kinase was isolated and well-characterized [149]. Furthermore, knockout of the MVA pathway genes of _Streptococcus pneumoniae_ stopped the growth in vitro under standard conditions. The growth was restored by adding mevalonate to the culture medium, demonstrating that this pathway is essential in this pathogenic bacterium and might represent a target for new antimicrobial compound [150]. The MEP is diffused in bacteria and plants. MVA and MEP coexist in eukaryotic organisms equipped with a plastid that evolved from a photosynthetic microorganism similar to modern-day cyanobacteria, according to the endosymbiotic theory [151]. These pieces of evidence suggest that MEP is characteristic of prokaryotes, and it was later acquired by eukaryotes with the photosynthetic endosymbiont, although different origins have been proposed [152]. Figure 5: Terpene and terpenoids biosynthesis. The precursors for biosynthesis of terpen and terpenoids (isopentyl-pyroP, IPP and dimethylallyl-piroP, DMAPP) are synthetized by two biosynthetic pathways: The mevalonate pathway (MVA, in red) and the methylerythnitol phosphate pathway (MEP, in green). As shown in the the square with blue dotted line, MVA was found in eukaryotes and archaea, while MEP was found in bacteria or in eukaryotes equipped with plastid. Horizontal gene exchange has allowed the acquisition of MVA (for the bacteria) or MEP genes (for the eukaryotes). GPS (geranyl-pyroP synthase), FPS (farnesyl-pyroP synthase) and GGPS (geranylgeranyl-pyroP synthase)  
assemble IPP and DMAPP into linear long-chain precursors used by the biosynthetic enzymes to produce the terpenes-like ring. In the figure, the examples are reported (from precursor to ring cyclization), including monoterpene synthases, diterpene synthases, and sesquiterpene synthases. Abbreviations: MVA: AACT = acetoacetyl-CoA thiolase, HMGS = 3-hydroxy-3-methylglutaryl-CoA synthase, HMGR = 3-hydroxy-3-methylglutaryl- CoA reductase, MVK = mevalonate kinase, PMK = phosphomevalonate kinase, MDC = mevalonate - 5-decarboxylate. Abbreviation of MEP: DXS = 1-deoxy-p-xylulose-5-phosphate synthase, DXP = deoxy-p-xylulose-5-phosphate, DXR = 1-deoxy-p-xylulose-5- reductase; MEP = methyl-erythitol phosphate, CMS = MEP cytidylyltransferase, CDP-MEP = cytidyllyl-MEP, MCS = ME-cpp synthase, ME-cpp = methyl-erythitol 2,4-cyclodiphosphate (ME-cpp), HDS = hydroxymethylbutenyl 4-diphosphate synthase, HMBPP = hydroxymethylbutenyl 4-diphosphate, IDS = IPP/DMAPP synthase, IDI/IDI2 = IPP-DAMPP isomerase.