A Glimpse into the Biosynthesis of Terpenoids

Abdallah, Ingy I; Quax, Wim J.

doi:10.18502/kls.v3i5.981

Cited by 55 publications

(39 citation statements)

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“…These are (1) geranyl pyrophosphate (GPP; C 10 ) produced by geranyl pyrophosphate synthase (GPPS) for the synthesis of monoterpenoids, (2) farnesyl pyrophosphate (FPP; C 15 ) produced by farnesyl pyrophosphate synthase (FPPS) for the construction of sesquiterpenoids and triterpenoids, and (3) geranylgeranyl pyrophosphate (GGPP; C 20 ) synthesized by geranylgeranyl pyrophosphate synthase (GGPPS) for the production of diterpenoids and tetraterpenoids. Finally, these starting precursors are cyclized and/or rearranged by terpene synthase enzymes to yield the different terpenoids (Withers and Keasling, 2007; Muntendam et al., 2009; Abdallah and Quax, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…The GGPP precursor can be synthesized via the MVA and/or the MEP pathway as previously explained. Taxadiene is converted to the final product, paclitaxel, through approximately 19 enzymatic steps involving hydroxylation and other oxygenation reactions of the taxadiene skeleton (Hezari and Croteau, 1997; Julsing et al., 2006; Abdallah and Quax, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Engineering of Bacillus subtilis Toward Taxadiene Biosynthesis as the First Committed Step for Taxol Production

et al. 2019

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Terpenoids are natural products known for their medicinal and commercial applications. Metabolic engineering of microbial hosts for the production of valuable compounds, such as artemisinin and Taxol, has gained vast interest in the last few decades. The Generally Regarded As Safe (GRAS) Bacillus subtilis 168 with its broad metabolic potential is considered one of these interesting microbial hosts. In the effort toward engineering B. subtilis as a cell factory for the production of the chemotherapeutic Taxol, we expressed the plant-derived taxadiene synthase (TXS) enzyme. TXS is responsible for the conversion of the precursor geranylgeranyl pyrophosphate (GGPP) to taxa-4,11-diene, which is the first committed intermediate in Taxol biosynthesis. Furthermore, overexpression of eight enzymes in the biosynthesis pathway was performed to increase the flux of the GGPP precursor. This was achieved by creating a synthetic operon harboring the B. subtilis genes encoding the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway ( dxs , ispD , ispF , ispH , ispC , ispE , ispG ) together with ispA (encoding geranyl and farnesyl pyrophosphate synthases) responsible for providing farnesyl pyrophosphate (FPP). In addition, a vector harboring the crtE gene (encoding geranylgeranyl pyrophosphate synthase, GGPPS, of Pantoea ananatis ) to increase the supply of GGPP was introduced. The overexpression of the MEP pathway enzymes along with IspA and GGPPS caused an 83-fold increase in the amount of taxadiene produced compared to the strain only expressing TXS and relying on the innate pathway of B. subtilis . The total amount of taxadiene produced by that strain was 17.8 mg/l. This is the first account of the successful expression of taxadiene synthase in B. subtilis . We determined that the expression of GGPPS through the crtE gene is essential for the formation of sufficient precursor, GGPP, in B. subtilis as its innate metabolism is not efficient in producing it. Finally, the extracellular localization of taxadiene production by overexpressing the complete MEP pathway along with IspA and GGPPS presents the prospect for further engineering aiming for semisynthesis of Taxol.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Engineering of Bacillus subtilis Toward Taxadiene Biosynthesis as the First Committed Step for Taxol Production

et al. 2019

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“…Based on our observation we propose that the genus Planococcus produces terpene containing BS through non-mevalonate pathway. It has been suggested that the terpene synthases are mainly responsible in contributing the diversity as well as complexity of the metabolites produced by the microbial system (Abdallah and Quax, 2017).…”

Section: Discussionmentioning

confidence: 99%

Genomic Insights of Halophilic Planococcus maritimus SAMP MCC 3013 and Detail Investigation of Its Biosurfactant Production

et al. 2019

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Moderate halophilic bacteria thrive in saline conditions and produce biosurfactant (BS) which facilitates the oil scavenging activity in the oil polluted surroundings. Production of such unusual bioactive molecules plays a vital role for their survival in an extreme and adverse environment. Current research deals with isolation of Planococcus maritimus strain SAMP MCC 3013 from Indian Arabian coastline sea water for BS production. The bacterium tolerated up to 2.7 M NaCl demonstrating osmotic stress bearable physiological systems. We used integrated approach to explore the genomic insight of the strain SAMP and displayed the presence of gene for BS biosynthesis. The genome analysis revealed this potential to be intrinsic to the strain. Preliminary screening techniques viz., surface tension (SFT), drop collapse (DC) and oil displacement (OD) showed SAMP MCC 3013 as a potent BS producer. BS reduced SFT of phosphate buffer saline (PBS) pH: 7.0 from 72 to 30 mN/m with a critical micelle concentration (CMC) value of 1.3 mg/mL. Subsequent investigation on chemical characterization, using thin layer chromatography (TLC), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance ( 1 H NMR and 13 C NMR) and liquid chromatography mass spectrometry (LC-MS) revealed terpene containing BS having sugar, lipid moieties. The genomic sequence analysis of P. maritimus SAMP showed complete genes in the pathway for the synthesis of terpenoid. Probably terpenoid is the accountable backbone molecule for the BS production, but the later stages of terpenoid conversion to the BS could not be found. Moreover, it is important to highlight that till today; no single report documents the in-detailed physico-chemical characterization of BS from Planococcus sp. Based on genomic and functional properties, the term terpene containing BS is denoted for the surfactant produced by P. maritimus .

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“…Terpene synthases perform complex chemical rearrangements leading to the production of terpenoids. The structural diversity of terpenoids is centered on the positioning of their substrate in the active site of the terpene synthase so it can undergo the required cyclizations and/or modifications to give the desired structure of the final product (1,2). Terpene synthases generally, and sesquiterpene synthases precisely, perform intricate catalytic mechanisms to produce their final product.…”

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confidence: 99%