Terpenoid Biosynthesis in Prokaryotes

Boronat, Albert; Rodríguez‐Concepción, Manuel

doi:10.1007/10_2014_285

Cited by 40 publications

(53 citation statements)

References 64 publications

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“…The genomes reconstructed in this study appear to contain putative polyketide synthases (PKS) involved in cell signalling and colonization of the dinoflagellate host, as well as terpenes (Supporting Information Table S5 and Fig. S2), which can act as precursors for hopanoid and carotenoid biosynthesis (Boronat and Rodríguez‐Concepción, ). This family of multidomain enzymes synthesizes a staggering variety of secondary metabolites of diverse structure and function (Jenke‐Kodama et al ., ).…”

Section: Resultsmentioning

confidence: 97%

Metabolic relationships of uncultured bacteria associated with the microalgae Gambierdiscus

Rambo

Dombrowski

Constant

et al. 2019

Environmental Microbiology

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Microbial communities inhabit algae cell surfaces and produce a variety of compounds that can impact the fitness of the host. These interactions have been studied via culturing, single-gene diversity and metagenomic read survey methods that are limited by culturing biases and fragmented genetic characterizations. Higher-resolution frameworks are needed to resolve the physiological interactions within these algalbacterial communities. Here, we infer the encoded metabolic capabilities of four uncultured bacterial genomes (reconstructed using metagenomic assembly and binning) associated with the marine dinoflagellates Gambierdiscus carolinianus and G. caribaeus. Phylogenetic analyses revealed that two of the genomes belong to the commonly algae-associated families Rhodobacteraceae and Flavobacteriaceae. The other two genomes belong to the Phycisphaeraceae and include the first algae-associated representative within the uncultured SM1A02 group. Analyses of all four genomes suggest these bacteria are facultative aerobes, with some capable of metabolizing phytoplanktonic organosulfur compounds including dimethylsulfoniopropionate and sulfated polysaccharides. These communities may biosynthesize compounds beneficial to both the algal host and other bacteria, including iron chelators, B vitamins, methionine, lycopene, squalene and polyketides. These findings have implications for marine carbon and nutrient cycling and provide a greater depth of understanding regarding the genetic potential for complex physiological interactions between microalgae and their associated bacteria.

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Section: Resultsmentioning

confidence: 97%

Metabolic relationships of uncultured bacteria associated with the microalgae Gambierdiscus

Rambo

Dombrowski

Constant

et al. 2019

Environmental Microbiology

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“…IPP and DMAPP, derived from the acetate-mevalonate or methylerythritol phosphate pathway (Boronat and Rodriguez-Concepcion 2015;Chang et al 2013;Zhao et al 2013), serve as precursors for prenyl diphosphate (nxC 5 ) biosynthesis (Oldfield and Lin 2012). The prenyl diphosphates can be used for the biosynthesis of different terpenoids by cyclization and oxidation or as prenyl donors for peptide, protein and tRNA prenyltransferases, or aromatic prenyltransferases.…”

Section: Classification Of Prenyltransferasesmentioning

confidence: 99%

“…Members of this enzyme group are involved in the biosynthesis of both primary metabolites such as ubiquinones and menaquinones (Boronat and Rodriguez-Concepcion 2015;Meganathan and Kwon 2009) and secondary metabolites like microbial and plant natural products (Holm et al 2014;Wang et al 2014;Yazaki et al 2009;Zeyhle et al 2014a, b).…”

Section: Membrane-bound Prenyltransferases For Aromatic Substratesmentioning

confidence: 99%

Prenyltransferases as key enzymes in primary and secondary metabolism

Winkelblech

Fan

2015

Appl Microbiol Biotechnol

146

167

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Attachment of isoprene units to various acceptors by prenylation plays an important role in primary and secondary metabolism of living organisms. Protein prenylation belongs to posttranslational modification and is involved in cellular regulation process. Prenylated secondary metabolites usually demonstrate promising biological and pharmacological activities. Prenyl transfer reactions catalyzed by prenyltransferases represent the key steps in the biosynthesis and contribute significantly to the structural and biological diversity of these compounds. In the last decade, remarkable progress has been achieved in the biochemical, molecular, and structural biological investigations of prenyltransferases, especially on those of the members of the dimethylallyltryptophan synthase (DMATS) superfamily. Until now, more than 40 of such soluble enzymes are identified and characterized biochemically. They catalyze usually regioselective and stereoselective prenylations of a series of aromatic substances including tryptophan, tryptophan-containing peptides, and other indole derivatives as well as tyrosine or even nitrogen-free substrates. Crystal structures of a number of prenyltransferases have been solved in the past 10 years and provide a solid basis for understanding the mechanism of prenyl transfer reactions.

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“…The native mevalonate (MVA) and 2C‐methyl‐ d ‐erythritol‐4‐phosphate pathways both have multiple cofactor requirements including NAD(P)H and ATP/cytosine triphosphate (CTP). Furthermore, the direct precursors to these pathways, acetyl‐CoA, pyruvate, and glyceraldehyde‐3‐phosphate are not bulk chemicals making them unsuitable for cell‐free synthesis on their own (Boronat & Rodríguex‐Concepción, ). To use a low‐cost feedstock like glucose, glycolysis enzymes must also be included along with terpene pathway enzymes to precisely balance cofactor generation and utilization steps.…”

Section: Introductionmentioning

confidence: 99%

Cell free biosynthesis of isoprenoids from isopentenol

Ward

Chatzivasileiou

Stephanopoulos

2019

Biotech & Bioengineering

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Cell-free systems are growing in importance for the biosynthesis of complex molecules. These systems combine the precision of traditional chemistry with the versatility of biology in creating superior overall processes. Recently, a new synthetic pathway for the biosynthesis of isoprenoids using the substrate isopentenol, dubbed the isopentenol utilization pathway (IUP), was demonstrated to be a promising alternative to the native 2C-methyl-D-erythritol-4-phosphate (MEP) and mevalonate (MVA) pathways. This simplified pathway, which contains a minimum of four enzymes to produce basic monoterpenes and only depends on ATP and isopentenol as substrates, allows for a highly flexible approach to the commercial synthesis of isoprenoid products. In this work, we use metabolic reconstitution to characterize this new pathway in vitro and demonstrate its use for the cell-free synthesis of mono-, sesquit-, and diterpenoids. Kinetic modeling and sensitivity analysis were also used to identify the most significant parameters for taxadiene productivity, and metabolic control analysis was employed to elucidate protein-level interactions within this pathway, which demonstrated that the IUP enzymatic system is primarily controlled by the concentration and kinetics of choline kinase (CK) and not regulated by any pathway intermediates. This is a significant advantage over the natural MEP or MVA pathways as it greatly simplifies future metabolic engineering efforts, both in vitro and in vivo, aiming at improving the kinetics of CK. Finally, we used the insights gathered to demonstrate an in vitro IUP system that can produce 220 mg/L of the diterpene taxadiene, in 9 hr, almost 3-fold faster than any system reported thus far. K E Y W O R D Sbiocatalysis, enzyme kinetics, isoprenoids, metabolic control analysis, taxadiene

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Terpenoid Biosynthesis in Prokaryotes

Cited by 40 publications

References 64 publications

Metabolic relationships of uncultured bacteria associated with the microalgae Gambierdiscus

Metabolic relationships of uncultured bacteria associated with the microalgae Gambierdiscus

Prenyltransferases as key enzymes in primary and secondary metabolism

Cell free biosynthesis of isoprenoids from isopentenol

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