ミリグラムスケールでのエトポシド中間物質の生産のための総生物合成
Journal of the American Chemical Society
|November 23, 2019
まとめ
研究 者 たち は,がん 薬 エトポシド の 主要 な 前駆体 で ある (-) - デオキシポドフィロトキシン を 生産 する よう たばこ の 植物 を 設計 し まし た. この生物合成アプローチは 不足に直面している現在の方法に 信頼性の高い代替手段を提供します
科学分野:
- 植物バイオテクノロジー
- メタボリック・エンジニアリング
- 自然製品の生物合成
背景:
- エトポシドは重要な植物由来化学療法剤です
- 現在のエトポシドの生産はヒマラヤのマヤリンゴの半合成に依存し,サプライチェーンの脆弱性に直面しています.
- エトポシド前駆体のための信頼性のある,スケーラブルな製造方法が必要です.
研究 の 目的:
- エトポシドアグリコンの後期前駆体である (-) - デオキシポドフィロトキシンを生産するための信頼できる方法の確立.
- タバコの原料の生産のための生合成経路を設計する.
- 伝統的な抽出方法に伴う限界を克服する
主な方法:
- 16の遺伝子の一時的な発現によって 遺伝子組み換えたばこ植物
- メイアップルのコニフェリルアルコールの供給とエトポシドアグリコン経路酵素の組み込み遺伝子
- 多段階の生体合成経路の生産用チェーシとして使用されたタバコ.
主要な成果:
- 製造されたタバコの葉で (-) -デオキシポドフィロトキシンをミリグラムスケールで生成した.
- 乾燥した植物重量4. 3mgまで (-) - デオキシポドフィロトキシンを蓄積した.
- 高純度 (-) - デオキシポドフィロトキシンを乾燥植物重量0.71 mg/gまでの濃度で分離した.
結論:
- 長い生物合成経路 (>10段階) をたばこ生産システムに効率的に転送することが実証されています.
- 有用な化学療法用前駆体へのアクセスのための有効なミリグラムスケールの総生物合成を確立しました.
- エトポシド前駆体生産に 持続可能で信頼性の高い代替手段を提供しました
関連する概念動画
Fates of Pyruvate
12.3K
Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
12.3K
Overview of Fatty Acid Metabolism
37.8K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
37.8K
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Overview
22.4K
The Fischer esterification reaction was developed by the German chemist Emil Fischer in 1895. It is a condensation reaction between carboxylic acids and alcohols in an acidic medium to give esters and water.
22.4K
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
4.9K
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an...
4.9K
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
11.7K
Carboxylic acids react with alcohols to yield esters via an acid-catalyzed condensation reaction called Fischer esterification. This is a nucleophilic acyl substitution reaction that proceeds via a tetrahedral intermediate, where a water molecule is eliminated as the leaving group.
11.7K
Production of Organic Acids
74
Lactic acid, an important organic acid extensively applied in food, pharmaceutical, and biodegradable polymer industries, is primarily produced via microbial fermentation. This method is favored over chemical synthesis due to its environmental sustainability and capacity for enantiomerically pure product formation. Among various microbial processes, the fermentation of starch-based substrates stands out due to the abundance and renewability of raw materials like corn and potatoes.Hydrolysis of...
74


