Biosynthesis of paclitaxel using synthetic biology

Tong, Yuru; Luo, Yunfeng; Gao, Wei

doi:10.1007/s11101-021-09766-0

Cited by 17 publications

(13 citation statements)

References 99 publications

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“…Synthetic biology aims to redesign metabolic pathways and broaden the spectrum of products (e.g., protocatechuic acid, paclitaxel, opioids) ( Guan et al, 2020 ; Tong et al, 2021 ; Zhang et al, 2021 ). However, the new substrates and products usually affect the performance of these artificial cell factories.…”

Section: Adaptation To Improve Microbial Performancementioning

confidence: 99%

Microbial Adaptation to Enhance Stress Tolerance

et al. 2022

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Microbial cell factories have been widely used in the production of various chemicals. Although synthetic biology is useful in improving the cell factories, adaptation is still widely applied to enhance its complex properties. Adaptation is an important strategy for enhancing stress tolerance in microbial cell factories. Adaptation involves gradual modifications of microorganisms in a stressful environment to enhance their tolerance. During adaptation, microorganisms use different mechanisms to enhance non-preferred substrate utilization and stress tolerance, thereby improving their ability to adapt for growth and survival. In this paper, the progress on the effects of adaptation on microbial substrate utilization capacity and environmental stress tolerance are reviewed, and the mechanisms involved in enhancing microbial adaptive capacity are discussed.

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Section: Adaptation To Improve Microbial Performancementioning

confidence: 99%

Microbial Adaptation to Enhance Stress Tolerance

et al. 2022

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“…Accordingly, the Taxol supply problem has now been completely solved by these two approaches. The topic of Taxol production has also been discussed in several reviews, ,− and this section has thus been abbreviated.…”

Section: Introductionmentioning

confidence: 99%

Strategies and Lessons Learned from Total Synthesis of Taxol

et al. 2023

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Taxol (paclitaxel), the most well-known taxane diterpenoid, is the best-selling natural-source anticancer drug ever produced and one of the most common prescriptions in the treatment of breast, lung, and ovarian cancers, saving countless lives around the world. Structurally, Taxol possesses a highly oxygenated [6−8−6−4] core bearing 11 stereocenters, seven of which are contiguous chiral centers. Moreover, the extremely strained bicyclo[5.3.1] undecane ring system with a bridgehead double bond is a unique structural feature. All these features make Taxol a highly challenging synthetic target. Tremendous synthetic efforts from more than 60 research groups around the world have already culminated in ten total syntheses and three formal syntheses, as well as more than 60 synthetic model studies of Taxol. This review is intended to provide a long-overdue appraisal of the great achievements in the total syntheses of Taxol reported in the last few decades. In doing so, we summarize the development of synthesis toward Taxol from 1994 to 2022, including the evolution of synthetic strategy for accessing this complex molecular scaffold and key lessons learned from such endeavors. Finally, we briefly discuss the future of the research in this area.

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“…Paclitaxel biosynthesis in Taxus is a complex metabolic pathway that requires at least 19 enzymatic steps and more than 20 enzymes [ 11 , 12 ]. To date, this pathway has 13 identified enzymes, including one taxadiene synthase (TS), which cyclizes the diterpenoid precursor geranylgeranyl diphosphate (GGPP) into taxadiene [ 13 ]; five cytochrome P450 (CYP450) hydroxylases (T5αH, T10βH, T2αH, T7βH, and T13αH) [ 14 – 16 ] and five acyltransferases (TAT, TBT, DBAT, BAPT, and DBTNBT) [ 17 – 19 ], which decorated the taxane skeleton to form the final product paclitaxel; and two enzymes (PAM and T2′OH) in the β-phenylalanoyl side chain [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis provides insights into light condition effect on paclitaxel biosynthesis in yew saplings

Liao

et al. 2022

BMC Plant Biol

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Background Taxus is a rare gymnosperm plant that is the sole producer of the anticancer drug paclitaxel. The growth and development of Taxus is affected by environmental factors such as light. However, little is known about how light conditions affect growth and metabolic processes, especially paclitaxel biosynthesis. Results In this study, we applied three different light conditions to Taxus chinensis young saplings and investigated the physiological response and gene expression. Our observations showed that exposure to high light led to oxidative stress, caused photoinhibition, and damaged the photosynthetic systems in T. chinensis. The paclitaxel content in T. chinensis leaves was significantly decreased after the light intensity increased. Transcriptomic analysis revealed that numerous genes involved in paclitaxel biosynthesis and phenylpropanoid metabolic pathways were downregulated under high light. We also analyzed the expression of JA signaling genes, bHLH, MYB, AP2/ERF transcription factors, and the CYP450 families that are potentially related to paclitaxel biosynthesis. We found that several CYP450s, MYB and AP2/ERF genes were induced by high light. These genes may play an important role in tolerance to excessive light or heat stress in T. chinensis. Conclusions Our study elucidates the molecular mechanism of the effects of light conditions on the growth and development of T. chinensis and paclitaxel biosynthesis, thus facilitating the artificial regeneration of Taxus and enhancing paclitaxel production.

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Biosynthesis of paclitaxel using synthetic biology

Cited by 17 publications

References 99 publications

Microbial Adaptation to Enhance Stress Tolerance

Microbial Adaptation to Enhance Stress Tolerance

Strategies and Lessons Learned from Total Synthesis of Taxol

Transcriptome analysis provides insights into light condition effect on paclitaxel biosynthesis in yew saplings

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