D-丙氨酸在细菌中的功能和代谢研究进展
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摘要
D?丙氨酸是L?丙氨酸的手性分子,在细菌个体中参与细胞壁肽聚糖和磷壁酸等的构成以及孢子的出芽和呼吸代谢等过程;在细菌群落中,D?丙氨酸参与生物膜的形成与调节。D?丙氨酸在细菌中的功能和代谢存在特异性,其代谢通路中的酶和基因可作为药物的靶向位点。本文对D?丙氨酸的合成,在细菌中的代谢及功能等方面的作用进行综述,探讨D?丙氨酸与变异链球菌致病性的关系,以期为抗龋药物候选靶向位点提供理论基础。通过现有研究结果表明,D?丙氨酸代谢过程中的酶及相关基因在对变异链球菌的生长及生物膜形成具有重要作用,有望作为靶点设计抗龋药物。
D?alanine is a chiral molecule of L?alanine that participates in the formation and regulation of cell wall peptidoglycans, phosphoteichoic acid, spore germination and respiratory metabolism in individual bacteria. D?alanine participates in the formation and regulation of biofilm in bacterial communities. The function and metabolism of D?ala?nine in bacteria are specific, and the enzymes and genes in its metabolic pathway can be used as drug targeting sites. In this paper, the synthesis, metabolism and function of D?alanine in bacteria were reviewed, and the relationship between D?alanine and pathogenicity of Streptococcus mutans was discussed to provide a theoretical basis for candidate targeting sites of anti?caries drugs. According to existing research results, the enzymes and related genes involved in D?alanine metabolism play important roles in the growth and biofilm formation of Streptococcus mutans, and D?alanine is expected to be a target for the design of anti?caries drugs.
D?alanine is a chiral molecule of L?alanine that participates in the formation and regulation of cell wall peptidoglycans, phosphoteichoic acid, spore germination and respiratory metabolism in individual bacteria. D?alanine participates in the formation and regulation of biofilm in bacterial communities. The function and metabolism of D?ala?nine in bacteria are specific, and the enzymes and genes in its metabolic pathway can be used as drug targeting sites. In this paper, the synthesis, metabolism and function of D?alanine in bacteria were reviewed, and the relationship between D?alanine and pathogenicity of Streptococcus mutans was discussed to provide a theoretical basis for candidate targeting sites of anti?caries drugs. According to existing research results, the enzymes and related genes involved in D?alanine metabolism play important roles in the growth and biofilm formation of Streptococcus mutans, and D?alanine is expected to be a target for the design of anti?caries drugs.
引文
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[24] Qiu W, Zheng X, Wei Y, et al. d?Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans[J]. Mol Oral Microbiol, 2016, 31(5):435?444.
[25] Halouska S, Fenton RJ, Zinniel DK, et al. Metabolomics analysis identifies d?Alanine?d?Alanine ligase as the primary lethal target of d?Cycloserine in mycobacteria[J]. J Proteome Res, 2014, 13(2):1065?1076.
[26] Moscoso M, García P, Cabral MP, et al. A D?Alanine auxotrophic live vaccine is effective against lethal infection caused by Staphy?lococcus aureus[J]. Virulence, 2018, 9(1):604?620.
[27] Wei Y, Qiu W, Zhou XD, et al. Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mu?tans[J]. Int J Oral Sci, 2016, 8(4):231?238.
[28] Liu S, Wei Y, Zhou X, et al. Function of alanine racemase in the physiological activity and cariogenicity of Streptococcus mutans[J]. Sci Rep, 2018, 8(1):5984.
[2] Alt J, Rojas C, Wozniak K, et al. Development of a high?through?put method for the determination of pharmacological levels of plas?ma D?serine[J]. Anal Biochem, 2011, 419(2):106?109.
[3] Santillo A, Falvo S, Chieffi P, et al. D?Aspartate induces prolifera?tive pathways in spermatogonial GC?1 cells[J]. J Cell Physiol,2016, 231(2):490?495.
[4] Alvarez L, Espaillat A, Hermoso JA, et al. Peptidoglycan remodel?ing by the coordinated action of multispecific enzymes[J]. Microb Drug Resist, 2014, 20(3):190?198.
[5] Tanner ME. Understanding nature's strategies for enzyme?cata?lyzed racemization and epimerization[J]. Acc Chem Res, 2002, 35(4):237?246.
[6] Liu JL, Liu XQ, Shi YW. Expression, purification, and character?ization of alanine racemase from Pseudomonas putida YZ?26[J].World J of Microbiol Biotechnol, 2012, 28(1):267?274.
[7] He W, Li C, Lu CD. Regulation and characterization of the dadRAX locus for D?amino acid catabolism in Pseudomonas aeru?ginosa PAO1[J]. J Bacteriol Mycol, 2011, 193(9):2107.
[8] Rossignoli G, Phillips RS, Astegno A, et al. Phosphorylation of pyridoxal 5'?phosphate enzymes:an intriguing and neglected topic[J]. Amino Acids, 2017, 50(1):205?215.
[9] Watanabe A, Yoshimura T, Mikami B, et al. Reaction mechanism of alanine racemase from Bacillus stearothermophilus:x?ray crys?tallographic studies of the enzyme bound with N?(5'?phosphopyri?doxyl)alanine[J]. J Biol Chem, 2002, 277(21):19166?19172.
[10] Watanabe A, Kurokawa Y, Yoshimura T, et al. Role of lysine 39 of alanine racemase from Bacillus stearothermophilus that binds pyri?doxal 5'?phosphate[J]. J Biol Chem, 1999, 274(7):4189?4194.
[11] Watanabe A, Yoshimura T, Mikami B, et al. Tyrosine 265 of Ala?nine Racemase serves as a base abstractingα?hydrogen from L?Al?anine:the counterpart residue to Lysine 39 Specific to D?Alanine[J]. J Biochem, 1999, 126(4):781?786.
[12] Nagata K, Nagata Y, Sato T, et al. L?Serine, D?and L?proline and alanine as respiratory substrates of Helicobacter pylori:correlation between in vitro and in vivo amino acid levels[J]. Microbiology,2003, 149(8):2023?2030.
[13] Tanigawa M, Shinohara T, Saito M, et al. D?Amino acid dehydroge?nase from Helicobacter pylori NCTC 11637[J]. Amino Acids,2010, 38(1):247?255.
[14] Vollmer W, Blanot D, de Pedro MA. Peptidoglycan structure and architecture[J]. FEMS Microbiol Rev, 2008, 32(2):149?167.
[15] Typas A, Banzhaf M, Gross CA, et al. From the regulation of pepti?doglycan synthesis to bacterial growth and morphology[J]. Nat Rev Microbiol, 2012, 10(2):123?136.
[16] Schneewind O, Missiakas D. Lipoteichoic acids, phosphate?con?taining polymers in the envelope of gram?positive bacteria[J]. J Bacteriol, 2014, 196(6):1133?1142.
[17] Auer GK,Weibel DB. Bacterial cell mechanics[J]. Biochemistry,2017, 56(29):3710?3724.
[18] Boyd DA, Cvitkovitch DG, Bleiweis AS, et al. Defects in D?alanyl?lipoteichoic acid synthesis in Streptococcus mutans results in acid sensitivity[J]. J Bacteriol, 2000, 182(21):6055?6065.
[19] Kamar R, Réjasse A, Jéhanno I, et al. DltX of Bacillus thuringien?sis is essential for D?Alanylation of teichoic acids and resistance to antimicrobial response in insects[J]. Front Microbiol, 2017, 8:1437.
[20] Zhu D, Sorg JA, Sun X. Clostridioides difficile biology:sporula?tion, germination, and corresponding therapies for infection[J].Front Cell Infect Microbiol, 2018, 8:29.
[21] Hills GM. Chemical factors in the germination of spore?bearing aerobes; the effect of yeast extract on the germination of Bacillus anthracis and its replacement by adenosine[J]. Biochem J, 1949,45(3):353?362.
[22] Atluri S, Ragkousi K, Cortezzo DE, et al. Cooperativity between different nutrient receptors in germination of spores of Bacillus subtilis and reduction of this cooperativity by alterations in the GerB receptor[J]. J Bacteriol, 2006, 188(1):28?36.
[23] Venir E, Del Torre M, Cunsolo V, et al. Involvement of alanine ra?cemase in germination of Bacillus cereus spores lacking an intact exosporium[J]. Arch Microbiol., 2014, 196(2):79?85.
[24] Qiu W, Zheng X, Wei Y, et al. d?Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans[J]. Mol Oral Microbiol, 2016, 31(5):435?444.
[25] Halouska S, Fenton RJ, Zinniel DK, et al. Metabolomics analysis identifies d?Alanine?d?Alanine ligase as the primary lethal target of d?Cycloserine in mycobacteria[J]. J Proteome Res, 2014, 13(2):1065?1076.
[26] Moscoso M, García P, Cabral MP, et al. A D?Alanine auxotrophic live vaccine is effective against lethal infection caused by Staphy?lococcus aureus[J]. Virulence, 2018, 9(1):604?620.
[27] Wei Y, Qiu W, Zhou XD, et al. Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mu?tans[J]. Int J Oral Sci, 2016, 8(4):231?238.
[28] Liu S, Wei Y, Zhou X, et al. Function of alanine racemase in the physiological activity and cariogenicity of Streptococcus mutans[J]. Sci Rep, 2018, 8(1):5984.