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Two Cooperative Glycosyltransferases Are Responsible for the Sugar Diversity of Saquayamycins Isolated from Streptomyces sp. KY 40-1
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1021/acschembio.7b00453 Shaimaa M. Salem 1 , Stevi Weidenbach 1 , Jürgen Rohr 1
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1021/acschembio.7b00453 Shaimaa M. Salem 1 , Stevi Weidenbach 1 , Jürgen Rohr 1
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Glycosyltransferases are key enzymes involved in the biosynthesis of valuable natural products providing an excellent drug-tailoring tool. Herein, we report the identification of two cooperative glycosyltransferases from the sqn gene cluster directing the biosynthesis of saquayamycins in Streptomyces sp. KY40-1: SqnG1 and SqnG2. Gene inactivation of sqnG1 leads to 50-fold decrease in saquayamycin production, while inactivation of sqnG2 leads to complete production loss, suggesting that SqnG2 acts as dual O- and C-glycosyltransferase. Gene inactivation of a third putative glycosyltransferase-encoding gene, sqnG3, does not affect saquayamycin production in a major way, suggesting that SqnG3 has no or a supportive role in glycosylation. The data indicate that SqnG1 and SqnG2 are solely and possibly cooperatively responsible for the sugar diversity observed in saquayamycins 1–7. This is the first evidence of a glycosyltransferase system showing codependence to achieve dual O- and C-glycosyltransferase activity, utilizing NDP-activated d-olivose, l-rhodinose, as well as an unusual amino sugar, presumably 3,6-dideoxy-l-idosamine.
中文翻译：
两种合作的糖基转移酶负责从链霉菌属分离的Sa霉素的糖多样性。肯塔基州40-1
糖基转移酶是参与有价值的天然产物生物合成的关键酶，可提供出色的药物定制工具。在这里，我们报告了从sqn基因簇中鉴定两个协同糖基转移酶的鉴定，该基因簇指导链霉菌属细菌中sa霉素的生物合成。KY40-1：SqnG1和SqnG2。sqnG1的基因失活导致sa霉素产量降低50倍，而sqnG2的失活导致完全产量损失，这表明SqnG2充当O-和C-糖基转移酶。第三个推定的糖基转移酶编码基因sqnG3的基因失活SqnG3不会在很大程度上影响萨瓜霉素的产生，这表明SqnG3在糖基化中没有作用或没有支持作用。数据表明，SqnG1和SqnG2单独且可能对沙格霉素1–7中观察到的糖多样性起合作作用。这是表示相互依赖实现双重O-和C-糖基转移酶活，利用NDP活化糖基转移酶系统的第一个证据d -olivose，升-rhodinose，以及一个不寻常的氨基糖，大概是3,6-二脱氧升-氨基胺。
更新日期：2017-09-14
中文翻译：
两种合作的糖基转移酶负责从链霉菌属分离的Sa霉素的糖多样性。肯塔基州40-1
糖基转移酶是参与有价值的天然产物生物合成的关键酶，可提供出色的药物定制工具。在这里，我们报告了从sqn基因簇中鉴定两个协同糖基转移酶的鉴定，该基因簇指导链霉菌属细菌中sa霉素的生物合成。KY40-1：SqnG1和SqnG2。sqnG1的基因失活导致sa霉素产量降低50倍，而sqnG2的失活导致完全产量损失，这表明SqnG2充当O-和C-糖基转移酶。第三个推定的糖基转移酶编码基因sqnG3的基因失活SqnG3不会在很大程度上影响萨瓜霉素的产生，这表明SqnG3在糖基化中没有作用或没有支持作用。数据表明，SqnG1和SqnG2单独且可能对沙格霉素1–7中观察到的糖多样性起合作作用。这是表示相互依赖实现双重O-和C-糖基转移酶活，利用NDP活化糖基转移酶系统的第一个证据d -olivose，升-rhodinose，以及一个不寻常的氨基糖，大概是3,6-二脱氧升-氨基胺。
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