Synthetic Biology
Strain Engineering for Paclitaxel

Strain Engineering for Paclitaxel

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Strain Engineering for Paclitaxel

CD Biosynsis integrates genetic engineering, metabolic engineering, and synthetic biology strategies to design microorganisms that increase the yield of paclitaxel biosynthesis by overcoming the rate-limiting step of paclitaxel synthesis, reducing the metabolic flow to competing pathways, and decreasing paclitaxel catabolism.

Background

Paclitaxel is a rare diterpenoid with anticancer activity isolated from the bark of the redbud tree and is a first-line clinical drug widely used in the treatment of various cancers. At present, there are several methods to obtain paclitaxel: direct extraction from redbud, chemical total synthesis, chemical semi-synthesis, etc. Among them, chemical semi-synthesis is the most popular raw material for paclitaxel in the world. Among them, chemical semi-synthesis is the main way to provide paclitaxel API in the world. The content of paclitaxel in the bark of Sequoia trees is low, and the semi-synthetic method, which relies on the consumption of Sequoia resources, cannot meet the commercial demand. Chemical total synthesis methods have not been applied to industrial production so far due to their complex processes and many synthesis steps. Therefore, the construction of an artificial biosynthesis system for paclitaxel using biosynthesis technology is an important measure to solve the problem of paclitaxel production.

Figure 1. Overview of the Taxol biosynthetic pathway. (Croteau R, et al., 2006)Figure 1. Overview of the Taxol biosynthetic pathway. (Croteau R, et al., 2006)

What We Provide

Based on the basic clarification of the mechanism of paclitaxel biosynthesis using isopentenyl pyrophosphate and dimethyl propylenyl pyrophosphate as the dividing line, we developed an efficient paclitaxel biosynthesis strategy using synthetic biology technology.

Genetic Engineering

We are able to modify the paclitaxel synthesis pathway using genetic engineering tools to increase the yield of the paclitaxel intermediate or end product.

Metabolic Engineering

We are able to construct paclitaxel metabolic pathways or optimize paclitaxel synthesis pathways in microorganisms and use microbial factories for mass production of paclitaxel.

Computer-Aided Design

We are able to use computational models to predict the genes affecting the paclitaxel metabolic pathway, perform correlation analysis of target genes on paclitaxel synthesis, and obtain the relationship between target gene expression and paclitaxel production.

Precision Fermentation

We are able to increase the amount of endophytic fungal biosynthesis of paclitaxel by optimizing the fermentation culture conditions of high-yielding paclitaxel strains.

Deliverables

  • Efficient cell factory for paclitaxel production.
  • Paclitaxel.

How We Can Help

Development of Microbial Chassis for Paclitaxel Production

We are able to develop microbial chassis for a high yield of paclitaxel based on the mevalonate pathway and non-mevalonate pathway present in microorganisms with the help of synthetic biology techniques. The following are the microbial chassis that has been used for the production of paclitaxel. Please contact us directly if you have other chassis of interest for paclitaxel production.

Escherichia coli Saccharomyces cerevisiae

Development of Plant Chassis for Paclitaxel Production

Compared with microbial chassis, plant chassis have obvious advantages in terms of membrane protein expression, precursor supply, and product tolerance. However, the first step product of paclitaxel synthesis, paclitaxel diene, can currently only be produced in plant chassis. The following are the plant chassis that has been used for the production of paclitaxel.

Panax ginseng Lycopersicum esculentum Arabidopsis thaliana

Paclitaxel Production by Endophytic Fungus Fermentation

We are able to produce paclitaxel by fermentation of endophytic fungi based on the genetics and molecular biology techniques associated with endophytic fungi. The following table shows the endophytic fungi that we can provide for paclitaxel synthesis, and the specific services that we can provide in order to further improve the paclitaxel production from endophytic fungi are as follows.

Pestalotiopsis microspora Noduzisporium sylviforme Fusarium lateritium Alternaria Phomopsis
Tubercularia sp. Aspergillus niger var. Periconia sp. Monochaetia sp. Pithomyces sp.
Pestalotia bicilia Rhizoctonia sp. Phoma Botrytis sp. Papulaspora sp.
  • We are able to improve strains using physical mutagenesis, chemical mutagenesis, and conformational mutagenesis.
  • We are able to improve endophytic fungal paclitaxel production using protoplast fusion technology in combination with mutagenesis.
  • We are able to use genetic engineering techniques to construct fungal expression vectors carrying genes encoding key enzymes of the paclitaxel synthesis pathway to obtain engineered strains with high paclitaxel production.
  • We are able to improve the synthesis of endophytic fungal paclitaxel by optimizing the fermentation culture conditions by adding carbon sources, nitrogen sources, precursors, special inducers, inhibitors, etc.

Applications of Paclitaxel

CD Biosynsis can develop tailored tools and customized approaches to harness the power of synthetic biology to drive paclitaxel production and meet the needs of customers in a variety of industries.

  • For the treatment of breast cancer, endometrial cancer, non-small cell lung, bladder, and cervical cancer.
  • For the treatment of AIDS-related Kaposi's sarcoma.
  • For the treatment of Benign cicatricial airway stenosis.

Want to Learn More?

CD Biosynsis provides the most comprehensive and efficient solutions for synthetic biology workflows. We are committed to helping our customers solve all problems encountered in paclitaxel production to advance their applications in a wide range of fields. Each of our deliverables will undergo a rigorous quality inspection test to ensure the reliability and accuracy of the results. If you are interested in our services or have any further questions, please do not hesitate to contact us.

Reference

  1. Croteau R, et al. Taxol biosynthesis and molecular genetics. Phytochem Rev. 2006 Feb; 5(1): 75-97.
Please note that all services are for research use only. Not intended for any clinical use.

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