レトロカルコンの生物合成経路とメカニズムの解明

Lei Ye¹, Zi-Long Wang¹, Zi-Qi Xu¹

¹State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.

Journal of the American Chemical Society

|July 29, 2025

まとめ

研究者達はレトロカルコンの生体合成経路を発見しこの天然産物がどのように形成されるかを明らかにしました重要な酵素であるGinKR1とそのユニークな構造が特定され,エキナチンおよび関連する化合物の形成が説明されました.

科学分野:

自然製品化学
生物化学
植物分子生物学

背景:

薬の発見には重要な骨組みです
レトロカルコンは別種のカルコンで生物合成経路が難しい.
エキナチンは, *Glycyrrhiza inflata* のレトロカルコンであり,肝臓を保護する性質を示しています.

研究の目的:

レトロカルコンの生体合成経路を解明する
レトロカルコン形成に関与する重要な酵素とメカニズムを特定する.
レトロカルコン生物合成における酵素特異性の構造的基礎を理解する.

主な方法:

酵素の識別と特徴付け (ケトレデクタゼ GinKR1)
同位体ラベル (¹⁸O) で酸素の起源を特定する.
GinKR1の結晶構造の決定
同性遺伝子を特定するためのバイオ情報分析

主要な成果:

還元と脱水によるレトロカルコン骨格形成を触媒するケトレダクトーゼであるGinKR1を特定した.
通常のカルコーン (シキマートとポリケチド経路) と比較して,AとB環の逆生物合成が明らかになった.
¹⁸Oラベルによるフラバノン2ヒドロキシラーゼによるカルボニル酸素由来が確認された.
エキナチン生物合成の全6酵素経路を解明した.
GinKR1の結晶構造が決定され,地域選択性のためのα10ヘリクスを強調した.
185種の植物で同種のGinKR1遺伝子を発見した.

結論:

レトロカルコンの生物合成経路とメカニズムは解明されている.
GinKR1とそのα10ヘリクスは,地域選択的なレトロカルコン形成に不可欠である.
レトロカルコンの生物合成にはユニークな酵素のステップと経路の逆転が含まれています.

さらに関連する動画

07:59

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products

Published on: October 4, 2019

9.9K

06:31

Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators

Published on: November 27, 2015

9.7K

関連する概念動画

02:05

Prochirality

4.0K

The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...

4.0K

01:29

Biosynthesis of Lipids

Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...

01:32

Export of Misfolded Proteins out of the ER

3.9K

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

3.9K

01:33

Overview of Secretory Vesicles

8.6K

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...

8.6K

02:33

Hedgehog Signaling Pathway

7.5K

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

7.5K

02:32

Exon Recombination

3.7K

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...