Thiamin (Vitamin B1) Biosynthesis and Regulation: A Rich Source of Antimicrobial Drug Targets?

被引：132

作者：

Du, Qinglin ^{[1
]}

Wang, Honghai ^{[2
]}

Xie, Jianping ^{[1
,2
]}

机构：

[1] Southwest Univ, Inst Modern Biopharmaceut, Sch Life Sci,Gorges Area 3, State Key Lab Breeding Base Ecoenviroment & Biore, Chongqing 400715, Peoples R China

[2] Fudan Univ, Inst Genet, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2011年 / 7卷 / 01期

关键词：

thiamin biosynthesis; riboswitch; Mycobacterium tuberculosis; drug targets; NON-MEVALONATE PATHWAY; ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; ACETOHYDROXYACID SYNTHASE; PHOSPHATE SYNTHASE; ISOPRENOID BIOSYNTHESIS; COMPARATIVE GENOMICS; CRYSTAL-STRUCTURE; THIAZOLE MOIETY; GENE-EXPRESSION;

D O I：

10.7150/ijbs.7.41

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Drug resistance of pathogens has necessitated the identification of novel targets for antibiotics. Thiamin (vitamin B1) is an essential cofactor for all organisms in its active form thiamin diphosphate (ThDP). Therefore, its metabolic pathways might be one largely untapped source of antibiotics targets. This review describes bacterial thiamin biosynthetic, salvage, and transport pathways. Essential thiamin synthetic enzymes such as Dxs and ThiE are proposed as promising drug targets. The regulation mechanism of thiamin biosynthesis by ThDP riboswitch is also discussed. As drug targets of existing antimicrobial compound pyrithiamin, the ThDP riboswitch might serves as alternative targets for more antibiotics.

引用

页码：41 / 52

页数：12

共 90 条

[31] Design and Antimicrobial Action of Purine Analogues That Bind Guanine Riboswitches [J].

Kim, Jane N. ;

Blount, Kenneth F. ;

Puskarz, Izabela ;

Lim, Jinsoo ;

Link, Kristian H. ;

Breaker, Ronald R. .

ACS CHEMICAL BIOLOGY, 2009, 4 (11) :915-927

[32] Thiazole synthase from Escherichia coli -: An investigation of the substrates and purified proteins required for activity in vitro [J].

Kriek, Marco ;

Martins, Filipa ;

Leonardi, Roberta ;

Fairhurst, Shirley A. ;

Lowe, David J. ;

Roach, Peter L. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (24) :17413-17423

[33] Thiamine-regulated gene expression of Aspergillus oryzae thiA requires splicing of the intron containing a riboswitch-like domain in the 5′-UTR [J].

Kubodera, T ;

Watanabe, M ;

Yoshiuchi, K ;

Yamashita, N ;

Nishimura, A ;

Nakai, S ;

Gomi, K ;

Hanamoto, H .

FEBS LETTERS, 2003, 555 (03) :516-520

[34] Isoprenoid biosynthesis: The evolution of two ancient and distinct pathways across genomes [J].

Lange, BM ;

Rujan, T ;

Martin, W ;

Croteau, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (24) :13172-13177

[35] Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction [J].

Lawhorn, BG ;

Mehl, RA ;

Begley, TP .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2004, 2 (17) :2538-2546

[36] Prodrug thiamine analogs as inhibitors of the enzyme transketolase [J].

Le Huerou, Yvan ;

Gunawardana, Indram ;

Thomas, Allen A. ;

Boyd, Steven A. ;

de Meese, Jason ;

deWolf, Walter ;

Gonzales, Steven S. ;

Han, May ;

Hayter, Laura ;

Kaplan, Tomas ;

Lemieux, Christine ;

Lee, Patrice ;

Pheneger, Jed ;

Poch, Gregory ;

Romoff, Todd T. ;

Sullivan, Francis ;

Weiler, Solly ;

Wright, S. Kirk ;

Lin, Jie .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (02) :505-508

[37] 'Turning on' riboswitches to their antibacterial potential [J].

Lea, Charles R. ;

Piccirilli, Joseph A. .

NATURE CHEMICAL BIOLOGY, 2007, 3 (01) :15-17

[38] Thiamine biosynthesis in Escherichia coli:: isolation and initial characterisation of the ThiGH complex [J].

Leonardi, R ;

Fairhurst, SA ;

Kriek, M ;

Lowe, DJ ;

Roach, PL .

FEBS LETTERS, 2003, 539 (1-3) :95-99

[39] A trans-Acting Riboswitch Controls Expression of the Virulence Regulator PrfA in Listeria monocytogenes [J].

Loh, Edmund ;

Dussurget, Olivier ;

Gripenland, Jonas ;

Vaitkevicius, Karolis ;

Tiensuu, Teresa ;

Mandin, Pierre ;

Repoila, Francis ;

Buchrieser, Carmen ;

Cossart, Pascale ;

Johansson, Jorgen .

CELL, 2009, 139 (04) :770-779

[40] NAD(P) Biosynthesis Enzymes as Potential Targets for Selective Drug Design [J].

Magni, G. ;

Di Stefano, M. ;

Orsomando, G. ;

Raffaelli, N. ;

Ruggieri, S. .

CURRENT MEDICINAL CHEMISTRY, 2009, 16 (11) :1372-1390

← 1 2 3 4 5 6 7 8 9 →