Sialic Acid (N-Acetyl Neuraminic Acid) Utilization by Bacteroides fragilis Requires a Novel N-Acetyl Mannosamine Epimerase

Sialic Acid (N-Acetyl Neuraminic Acid) Utilization by Bacteroides fragilis Requires a Novel N-Acetyl Mannosamine Epimerase
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DOI:
10.1128/jb.00811-08
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发表时间:
2009-06-01
影响因子:
3.2
通讯作者:
Malamy, Michael H.
Malamy, Michael H.
中科院分区:
生物学3区
文献类型:
--
作者:
Brigham, Christopher;Caughlan, Ruth;Malamy, Michael H.

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我们的特点是nanLET操纵子在脆弱拟杆菌,其产品所需的唾液酸N-乙酰神经氨酸(NANA)作为碳源和能源的利用。操纵子的第一个基因是nanL,其编码将NANA切割成N-乙酰甘露糖胺(manNAc)和丙酮酸的醛缩酶。下一个基因nanE编码manNAc/N-乙酰葡糖胺(NAG)差向异构酶,有趣的是,与其他细菌NanE差向异构酶蛋白相比,它与真核生物的肾素结合蛋白具有更多的相似性。未磷酸化的manNAc是NanE的底物,而ATP是差向异构酶反应中的辅因子。操纵子的第三个基因是nanT,它与主要的转运蛋白促进剂超家族相似,最有可能是NANA转运蛋白。这些基因中任何一个的缺失都会消除B的能力。fragilis在NANA上生长。虽然B. fragilis通常不以manNAc作为唯一碳源生长,我们分离了一个B。fragilis突变株,可能是由于NAG转运蛋白突变所致;在该菌株中,manNAc转运和NAG转运均受到影响。在manNAc激活的菌株中,nanE差向异构酶基因或rokA己糖激酶基因(其产物磷酸化NAG)的缺失消除了manNAc上的生长。因此,B。fragilis具有一种新的NANA利用途径,我们发现在其他拟杆菌属物种中也发现了这种途径。
We characterized the nanLET operon in Bacteroides fragilis, whose products are required for the utilization of the sialic acid N-acetyl neuraminic acid (NANA) as a carbon and energy source. The first gene of the operon is nanL, which codes for an aldolase that cleaves NANA into N-acetyl mannosamine (manNAc) and pyruvate. The next gene, nanE, codes for a manNAc/N-acetylglucosamine (NAG) epimerase, which, intriguingly, possesses more similarity to eukaryotic renin binding proteins than to other bacterial NanE epimerase proteins. Unphosphorylated manNAc is the substrate of NanE, while ATP is a cofactor in the epimerase reaction. The third gene of the operon is nanT, which shows similarity to the major transporter facilitator superfamily and is most likely to be a NANA transporter. Deletion of any of these genes eliminates the ability of B. fragilis to grow on NANA. Although B. fragilis does not normally grow with manNAc as the sole carbon source, we isolated a B. fragilis mutant strain that can grow on this substrate, likely due to a mutation in a NAG transporter; both manNAc transport and NAG transport are affected in this strain. Deletion of the nanE epimerase gene or the rokA hexokinase gene, whose product phosphorylates NAG, in the manNAc-enabled strain abolishes growth on manNAc. Thus, B. fragilis possesses a new pathway of NANA utilization, which we show is also found in other Bacteroides species.