Third DWF1 paralog in Solanaceae, sterol Δ
            <sup>24</sup>
            -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Knoch, Eva; Sugawara, Satoko; Mori, Tetsuya; Poulsen, Carsten Stig; Fukushima, Atsushi; Harholt, Jesper; Fujimoto, Yoshinori; Umemoto, Naoyuki; Saito, Kazuki

doi:10.1073/pnas.1807482115

Cited by 51 publications

(34 citation statements)

References 61 publications

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“…The common feature of withanolides is an intact or rearranged ergostane with a highly structurally diverse side chain ( Figure 3 ). The pathways for withanolide biosynthesis have been well-studied, in particular for the arrangement of the side chain in recent years [ 24 , 25 , 26 ]. Though no genes or enzymes specifically responsible for taccalonolides biosynthesis have been characterized to date, the fact that taccalonolides, perulactones, and withanolides are co-isolated from various plants suggesting that they share the same upstream biosynthetic pathway [ 21 , 23 , 27 ].…”

Section: Structures Of Natural Taccalonolides (1987–2020)mentioning

confidence: 99%

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Chen

Winstead

et al. 2021

Cancers

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Microtubule stabilizing agents, such as paclitaxel, docetaxel, and cabazitaxel have been among the most used chemotherapeutic agents in the last decades for the treatment of a wide range of cancers in the clinic. One of the concerns that limit their use in clinical practice is their intrinsic and acquired drug resistance, which is common to most anti-cancer chemotherapeutics. Taccalonolides are a new class of microtubule stabilizers isolated from the roots of a few species in the genus of Tacca. In early studies, taccalonolides demonstrated different effects on interphase and mitotic microtubules from those of paclitaxel and laulimalide suggesting a unique mechanism of action. This prompts the exploration of new taccalonolides with various functionalities through the identification of minor constituents of natural origin and semi-synthesis. The experiments on the new highly potent taccalonolides indicated that taccalonolides possessed a unique mechanism of covalently binding to the microtubule. An X-ray diffraction analysis of a crystal of taccalonolides AJ binding to tubulin indicated that the covalent binding site is at β-tubulin D226. Taccalonolides circumvent all three mechanisms of taxane drug resistance both in vitro and in vivo. To improve the activity, the structure modification through semi-synthesis was conducted and the structure-activity relationships (SARs) was analyzed based on natural and semi-synthetical taccalonolides. The C22-C23 epoxide can significantly increase the antiproliferation potency of taccalonolides due to the covalent link of C22 and the carboxylic group of D226. Great progress has been seen in the last few years in the understanding of the mechanism of this class of microtube-stabilizing agents. This review summarizes the structure diversity, structure-activity relationships (SARs), mechanism of action, and in vivo activities of taccalonolides.

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Section: Structures Of Natural Taccalonolides (1987–2020)mentioning

confidence: 99%

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Chen

Winstead

et al. 2021

Cancers

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“…4 , Table 2 ) [ 77 ]. On the other hand, withanolides are a group of bioactive steroids mainly found in the Solanoideae family, and are believed to be synthesized from 24-methylenecholesterol [ 79 , 80 ]. The first step converting 24-methylenecholesterol towards the synthesis of withanolides has been very recently characterized to be catalyzed by a sterol Δ 24 -isomerase (24ISO) (Fig.…”

Section: Synthesis Of Steroids With Saturated C7–c8 Bondmentioning

confidence: 99%

Yeast as a promising heterologous host for steroid bioproduction

2020

Journal of Industrial Microbiology and Biotechnology

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With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroidproducing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes.

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“…Super- Agrobacterium ver. 3 was also effective in the agro-infiltration method (Hoshikawa et al, 2019; Knoch et al, 2019).…”

Section: Introductionmentioning

confidence: 98%

Super-Agrobacterium ver. 4: Improving the Transformation Frequencies and Genetic Engineering Possibilities for Crop Plants

et al. 2019

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Agrobacterium tumefaciens has been utilized for both transient and stable transformations of plants. These transformation methods have been used in fields such as breeding GM crops, protein production in plant cells, and the functional analysis of genes. However, some plants have significantly lower transient gene transfer and stable transformation rates, creating a technical barrier that needs to be resolved. In this study, Super-Agrobacterium was updated to ver. 4 by introducing both the ACC deaminase (acdS) and GABA transaminase (gabT) genes, whose resultant enzymes degrade ACC, the ethylene precursor, and GABA, respectively. A. tumefaciens strain GV2260, which is similar to other major strains (EHA105, GV3101, LBA4404, and MP90), was used in this study. The abilities of the Super-Agrobacterium ver. 4 were evaluated in Erianthus ravennae, Solanum lycopersicum “Micro-Tom,” Nicotiana benthamiana, and S. torvum. Super-Agrobacterium ver. 4 showed the highest T-DNA transfer (transient transformation) frequencies in E. ravennae and S. lycopersicum, but not in N. benthamiana and S. torvum. In tomato, Super-Agrobacterium ver. 4 increased the stable transformation rate by 3.6-fold compared to the original GV2260 strain. Super-Agrobacterium ver. 4 enables reduction of the amount of time and labor required for transformations by approximately 72%, and is therefore a more effective and powerful tool for plant genetic engineering and functional analysis, than the previously developed strains. As our system has a plasmid containing the acdS and gabT genes, it could be used in combination with other major strains such as EHA105, EHA101, LBA4404, MP90, and AGL1. Super-Agrobacterium ver. 4, could thus possibly be a breakthrough application for improving basic plant science research methods.

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Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Cited by 51 publications

References 61 publications

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Yeast as a promising heterologous host for steroid bioproduction

Super-Agrobacterium ver. 4: Improving the Transformation Frequencies and Genetic Engineering Possibilities for Crop Plants

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Third DWF1 paralog in Solanaceae, sterol Δ 24 -isomerase, branches withanolide biosynthesis from the general phytosterol pathway

Cited by 51 publications

References 61 publications

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Yeast as a promising heterologous host for steroid bioproduction

Super-Agrobacterium ver. 4: Improving the Transformation Frequencies and Genetic Engineering Possibilities for Crop Plants

Contact Info

Product

Resources

About

Third DWF1 paralog in Solanaceae, sterol Δ ²⁴ -isomerase, branches withanolide biosynthesis from the general phytosterol pathway