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The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review.
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2011-Jan-01 , DOI: 10.1038/ja.2010.139
Heinz G Floss , Tin-Wein Yu , Kenji Arakawa

The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.

中文翻译:

3-氨基-5-羟基苯甲酸(AHBA)的生物合成,这是安沙霉素和丝裂霉素抗生素中mC7N单元的前体。

综述了3-氨基-5-羟基苯甲酸(AHBA),安沙霉素和其他抗生素的前体形成的氨基shi酸酯途径。在这种生物合成中,已从其他基因组中招募了形成甘露胺的基因,以提供含氮前体。然后将Kanosamine磷酸化,并通过常见的细胞酶将其转化为1-deoxy-1-imino-erythrose 4-phosphate(形成氨基DAHP的基质)。经由5-脱氧-5-氨基脱氢奎宁酸和5-脱氧-5-氨基脱氢hydro草酸将其转化为AHBA。值得注意的是,吡ido醛磷酸酶AHBA合酶似乎具有两个催化功能:作为同型二聚体,它催化该途径中的最后一个反应,即5-脱氧-5-氨基脱氢shi草酸的芳构化,在与氧化还原酶RifL形成复合物的途径开始时,它催化UDP-3-酮-D-葡萄糖的转氨作用。AHBA合酶基因在新安沙霉素和其他AHBA衍生的天然产物的遗传筛选中也可作为有用的工具。
更新日期:2017-01-31
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