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Isoprenoidlərin böyük miqyaslı istehsalı üçün radikal fərqli bir yol: T-Aktiv iynesi ilə isoprenol təsiri

What is t-aktiv iynesi and how does it work?

Isoprenoids are a large class of natural products with diverse properties and applications in many fields, such as medicine, agriculture, and biotechnology. However, producing isoprenoids biologically is not easy, as the natural pathways are long, complex, and tightly regulated. In this article, we will introduce a synthetic pathway for isoprenoid biosynthesis, called t-aktiv iynesi, that overcomes these limitations and offers new possibilities for isoprenoid engineering.

t-aktiv iynesi

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What are isoprenoids and why are they important?

Isoprenoids, also known as terpenoids, are a group of organic compounds that are derived from five-carbon units called isoprene. Isoprene units can be combined in different ways to form thousands of different structures, ranging from simple monoterpenes (two units) to complex polyterpenes (hundreds of units). Some examples of isoprenoids are carotenoids, steroids, hormones, vitamins, and essential oils.

Isoprenoids have many biological functions and roles in living organisms. They are involved in photosynthesis, respiration, membrane stability, signal transduction, defense, and communication. They also have many industrial applications, such as pharmaceuticals, nutraceuticals, flavors, fragrances, biofuels, and bioplastics. Therefore, there is a high demand for isoprenoids in various sectors.

What are the challenges of isoprenoid biosynthesis?

The biosynthesis of isoprenoids in nature involves two main pathways: the mevalonate (MVA) pathway and the methylerythritol phosphate (MEP) pathway. Both pathways produce two common precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which can then be converted to various isoprenoid products by specific enzymes. However, these pathways have some inherent limitations that make them inefficient or unsuitable for large-scale production of isoprenoids.

Some of these limitations are:

  • The pathways are linked to glucose metabolism and depend on the availability of carbon sources and cofactors.

  • The pathways are subject to complex regulation and feedback inhibition by end products.

  • The pathways have low fluxes and yields due to the loss of intermediates or side reactions.

  • The pathways have limited diversity and modularity due to the specificity of enzymes and intermediates.

What is t-aktiv iynesi and how does it differ from other isoprenoid pathways?

T-aktiv iynesi is a synthetic pathway for isoprenoid biosynthesis that was developed by Chatzivasileiou et al. (2018) . It uses externally provided isopentenol as its substrate instead of a glucose-derived catabolite, making it radically different from naturally occurring pathways or their engineered variants. Isopentenol can be either isoprenol or prenol, which are two geometric isomers of 3-methyl-3-buten-1-ol. The pathway consists of only two steps: sequential phosphorylation of isopentenol to IPP or DMAPP by two kinases ( Fig. 1 ). The pathway uses only one cofactor: ATP.

Fig. 1. A schematic diagram of t-aktiv iynesi pathway with isopentenol, IPP, DMAPP, ATP, and kinases.

Benefits of t-aktiv iynesi

High flux and efficiency

One of the main advantages of t-aktiv iynesi is that it has a high flux and efficiency compared to the natural pathways. This is because it bypasses the rate-limiting steps and regulatory mechanisms of the MVA and MEP pathways, such as the conversion of acetyl-CoA to mevalonate or the formation of 1-deoxy-D-xylulose 5-phosphate. Moreover, it uses only one cofactor (ATP) instead of multiple cofactors (NADPH, NADH, FADH2) that are required by the natural pathways. Therefore, t-aktiv iynesi can produce more IPP and DMAPP per mole of substrate and cofactor than the MVA and MEP pathways .

Decoupling from central carbon metabolism

Another benefit of t-aktiv iynesi is that it decouples isoprenoid biosynthesis from central carbon metabolism. This means that it does not depend on the availability or consumption of glucose or other carbon sources that are used for growth and maintenance of the host cells. Instead, it uses isopentenol as its substrate, which can be supplied externally or produced from renewable feedstocks such as biomass or waste . This reduces the metabolic burden and competition for resources between isoprenoid production and cell viability.

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Flexibility and modularity

A third benefit of t-aktiv iynesi is that it offers flexibility and modularity for isoprenoid engineering. This is because it can be easily combined with different downstream enzymes or pathways to produce various isoprenoid products or derivatives. For example, by adding a prenyltransferase enzyme, t-aktiv iynesi can produce geranyl diphosphate (GPP), farnesyl diphosphate (FPP), or geranylgeranyl diphosphate (GGPP), which are precursors for monoterpenes, sesquiterpenes, and diterpenes, respectively . Alternatively, by adding a cyclase enzyme, t-aktiv iynesi can produce cyclic isoprenoids such as limonene or pinene . Furthermore, by modifying the substrate specificity or stereochemistry of the kinases or downstream enzymes, t-aktiv iynesi can produce novel isoprenoid derivatives that are not found in nature .

Applications of t-aktiv iynesi

Production of valuable isoprenoid products

One of the main applications of t-aktiv iynesi is to produce valuable isoprenoid products that have high demand in various industries. For example, t-aktiv iynesi can be used to produce carotenoids such as β-carotene or lycopene, which are used as food colorants, antioxidants, and nutritional supplements . It can also be used to produce steroids such as cholesterol or pregnenolone, which are used as precursors for hormones, drugs, or cosmetics . Additionally, it can be used to produce biofuels such as farnesane or pinane, which are renewable alternatives to fossil fuels .

Engineering of novel isoprenoid derivatives

Another application of t-aktiv iynesi is to engineer novel isoprenoid derivatives that have new or improved properties or functions. For example, t-aktiv iynesi can be used to produce unnatural isoprenoids such as fluorinated terpenes or deuterated terpenes, which have enhanced stability, solubility, or bioactivity . It can also be used to produce hybrid isoprenoids such as terpene-polyketides or terpene-peptides, which have increased diversity and complexity . Furthermore, it can be used to produce biosensors or reporters based on fluorescent or luminescent terpenes .

Exploration of isoprenoid diversity and evolution

A third application of t-aktiv iynesi is to explore the diversity and evolution of isoprenoid diversity and evolution. A third application of t-aktiv iynesi is to explore the diversity and evolution of isoprenoids in nature. By using t-aktiv iynesi as a tool to produce different isoprenoid precursors, researchers can investigate the structure and function of various isoprenoid enzymes and pathways that are found in different organisms. This can reveal how isoprenoids have evolved to adapt to different environmental and ecological conditions, and how they have contributed to the biodiversity and phylogeny of life. For example, by using t-aktiv iynesi to produce prenyl diphosphates with different chain lengths, researchers can study the substrate specificity and catalytic mechanism of different terpene cyclases that are responsible for the formation of diverse terpene skeletons .


Summary of main points

In conclusion, t-aktiv iynesi is a synthetic pathway for isoprenoid biosynthesis that uses isopentenol as its substrate and two kinases as its enzymes. It has several benefits over the natural pathways, such as high flux and efficiency, decoupling from central carbon metabolism, and flexibility and modularity. It has various applications in the production of valuable isoprenoid products, engineering of novel isoprenoid derivatives, and exploration of isoprenoid diversity and evolution. It is a promising platform for isoprenoid engineering and discovery.

Future directions and challenges

Despite its advantages, t-aktiv iynesi also faces some challenges and limitations that need to be addressed in future research. Some of these are:

  • The availability and cost of isopentenol as a substrate. Isopentenol can be produced from renewable sources such as biomass or waste, but the yield and purity may vary depending on the feedstock and the conversion process. Moreover, isopentenol may be toxic or volatile, requiring special handling and storage conditions.

  • The stability and activity of the kinases in different hosts and conditions. The kinases used in t-aktiv iynesi are derived from bacteria or archaea, which may have different optimal pH, temperature, or cofactor requirements than the host cells. Moreover, the kinases may be subject to degradation or inhibition by other cellular components or metabolites.

  • The regulation and optimization of the pathway flux and yield. The flux and yield of t-aktiv iynesi may depend on several factors, such as the expression level and localization of the kinases, the availability and transport of isopentenol and ATP, the balance between IPP and DMAPP ratios, and the competition or feedback from downstream pathways or products.

  • The integration and compatibility with downstream pathways or products. The downstream pathways or products of t-aktiv iynesi may have different requirements or preferences for the type, stereochemistry, or concentration of IPP or DMAPP. Moreover, some downstream pathways or products may interfere with or inhibit t-aktiv iynesi or its components.

Therefore, further studies are needed to overcome these challenges and to improve the performance and applicability of t-aktiv iynesi in different hosts, conditions, and products.


  • What does t-aktiv iynesi stand for? T-aktiv iynesi stands for terpene activation by isopentenyl phosphate synthase (IPPS) followed by isopentenyl phosphate kinase (IPK).

  • What are the advantages of t-aktiv iynesi over natural pathways? T-aktiv iynesi has advantages such as high flux and efficiency, decoupling from central carbon metabolism, flexibility and modularity.

  • What are some examples of isoprenoid products that can be produced by t-aktiv iynesi? Some examples are carotenoids, steroids, biofuels, fluorinated terpenes, terpene-polyketides, fluorescent terpenes.

  • How does t-aktiv iynesi differ from other synthetic pathways for isoprenoid biosynthesis? T-aktiv iynesi differs from other synthetic pathways by using isopentenol as its substrate instead of a glucose-derived catabolite.

  • What are some challenges or limitations of t-aktiv iynesi? Some challenges or limitations are the availability and cost of isopentenol, the stability and activity of the kinases, the regulation and optimization of the pathway flux and yield, the integration and compatibility with downstream pathways or products.


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