CYP725A4分子序列分析与结构建模

蒙海林 汪建峰 王勇 张嗣良 王小宁

doi:10.3969/j.issn.1000-565X.2011.05.027

华南理工大学学报(自然科学版) >

2011 , Vol. 39 >Issue 5: 154 - 159

DOI: https://doi.org/10.3969/j.issn.1000-565X.2011.05.027

生物工程

CYP725A4分子序列分析与结构建模

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1．华南理工大学生物科学与工程学院，广东广州 510006；2．中国科学院上海生命科学研究院合成生物学重点实验室，上海 200032；3．华东理工大学生物反应器工程国家重点实验室，上海 200237

蒙海林(1980-)，男，博士生，主要从事合成生物学研究

收稿日期: 2010-10-14

修回日期: 2011-02-11

网络出版日期: 2011-04-01

基金资助

国家自然科学基金资助项目(31070030)；上海市“浦江人才计划”项目(09PJ1403600)；上海市“科技创新行动计划”重大科技项目(10dzl910100)；中国科学院知识创新工程重大项目(KSCX2-EW-J-12)

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Sequence Analysis and Structure Modeling of CYP 725A4

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1. School of Biological Sciences and Engineering,South China University of Technology,Guangzhou 510006,Guangdong China; 2. Key Laboratory of Synthetic Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200032,China; 3. State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China

蒙海林(1980-)，男，博士生，主要从事合成生物学研究

Received date: 2010-10-14

Revised date: 2011-02-11

Online published: 2011-04-01

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摘要

CYP725A4在大肠杆菌等原核宿主中难以实现高效功能表达，是制约紫杉醇异源合成的瓶颈之一。文中利用生物信息学方法对该酶分子的序列进行疏水性和跨膜区分析，构建了其分子进化树，在此基础上用同源建模方法构建了其天然态以及切除N端跨膜区后的三级结构，并对CYP725A4实现功能表达所必需的辅助还原酶也进行了天然态和切除N端跨膜区后的三级结构建模。所构建的结构模型经PROCHECK验证具有较好的可靠性。

关键词： 生物信息学; 细胞色素P450酶; 序列分析; 分子建模; 功能表达

本文引用格式

蒙海林汪建峰王勇张嗣良王小宁 . CYP725A4分子序列分析与结构建模[J]. 华南理工大学学报(自然科学版), 2011 , 39(5) : 154 -159 . DOI: 10.3969/j.issn.1000-565X.2011.05.027

Abstract

The difficulty in functional expression of CYP725A4 in heterogeneous prokaryotic hosts such as E.coli is a key bottleneck of the heterologous biosynthesis of taxol.In this paper,bioinformatic strategies were employed to analyze the hydrophobic profile and the transmembrane helices of CYP 725A4 sequence,and a molecular phylogenetic tree of CYP 725A4 was constructed.Then,based on the results,the tertiary structures of native and N-terminal truncated CYP 725A4 were reconstructed via the homology modeling,and similar operations were performed for native and truncated versions of cytochrome P450 reductase used for the functional expression of CYP 725A4.PROCHECK results show that the constructed structure models are all reliable.

Key words： bioinformatics; cytochrome P450 hydroxylase; sequence analysis; molecular modeling; functional expression

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