Enediyne抗腫瘍抗生物質C-1027の生物合成のための (R) -ヴィシナル二酸化物中間体をサポートするSgcFエポキシードヒドロラーゼの特徴化
Shuangjun Lin1, Geoffrey P Horsman, Yihua Chen
1Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705-2222, USA.
Journal of the American Chemical Society
|October 28, 2009
まとめ
酵素SgcFは,エポキシド中間物質を処理することによって,抗腫瘍抗生物質C-1027を生成するために不可欠です. このエポキシドヒドロラゼは特定のダイオルを生成し,C-1027生物合成経路におけるその重要な役割を確認します.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 酵素学 酵素学とは
背景:
- C-1027は,アポプロテインとクロモフォールで構成されたクロモプロテイン抗腫瘍抗生物質です.
- C-1027染色体には,エネディイン核,デオキシアミノ糖,ベンゾクサゾリナート,ベータタイロシン誘導体が含まれています.
- C-1027染色体を組み立てるための収束生物合成戦略が提案されています.
研究 の 目的:
- C-1027生物合成遺伝子群からエポキシドヒドロラーゼSgcFを特徴付ける.
- C-1027染色体の生物合成におけるSgcFの役割を明らかにする.
- スタイレン酸化物シミュレータにおけるSgcF活動の地域およびステレオ特異性を調査する.
主な方法:
- 酵素SgcF.のインビトロ特性分析
- スタイレン酸化物を基質として使用した酵素分析を模倣する.
- DeltasgcF変異株のStreptomyces globisporus SB1010のC-1027産生に関する分析
主要な成果:
- SgcFは,スタイレン酸化物の地域およびステレオ特異的水解を触媒化し,近隣の二酸化物を形成します.
- DeltasgcF変異株はC-1027の生産が廃止されたことを示し,sgcFの重要な役割を確認しました.
- SgcFは好ましく (S) -ステロイン酸化物を (R) -フェニル近隣二酸化物に高効率で水解する (Km = 0.6 mM, kcat = 48 min-1).
- SgcFはまた, (R) -ステロイン酸化物を (R) -フェニル近隣二酸化物に水分解するが,効率は低い (Km = 2.0 mM, kcat = 4.3 min-1).
結論:
- SgcFはC-1027の生物合成において不可欠な役割を果たしています.
- C-1027染色体経路における重要な中間物質として (R) - ヴィシナル二酸化物が特定されています.
- SgcFによるエナチオコンバージェント水解は,エポキシド水溶解を工学的に開発する可能性を秘めています.
さらに関連する動画
関連する概念動画
03:00Preparation of Epoxides
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
02:26Base-Catalyzed Ring-Opening of Epoxides
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
02:24Acid-Catalyzed Ring-Opening of Epoxides
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
02:57Sharpless Epoxidation
The conversion of allylic alcohols into epoxides using the chiral catalyst was discovered by K. Barry Sharpless and is known as Sharpless epoxidation. The use of a chiral catalyst enables the formation of one enantiomer of the product in excess. This chiral catalyst is mainly a chiral complex of titanium tetraisopropoxide and tartrate ester (specific stereoisomer). The stereoisomer used in the chiral catalyst dictates the formation of the enantiomer of the product. In other words, the use of...
01:14Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Malonic ester synthesis is a method to obtain α substituted carboxylic acids from ꞵ-diesters such as diethyl malonate and alkyl halides.
02:38Structure and Nomenclature of Epoxides
Cyclic ethers are heterocyclic compounds with an oxygen atom in the ring along with carbon atoms. They are named depending on the number of carbon atoms present in their ring system. Cyclic ethers with a three-membered ring system are called “oxirane”, four-membered ring systems as “oxetane”, five-membered ring systems as “oxolane”, and six-membered ring systems as “oxane”. The cyclic structure of these rings imposes angle strain, and this strain is more in the ring having a smaller number of...