One-pot enzymatic synthesis of 2-deoxy-scyllo-inosose from d-glucose and polyphosphate
One-pot enzymatic synthesis of 2-deoxy-scyllo-inosose from d-glucose and polyphosphate
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DOI：
10.1093/bbb/zbaa025
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发表时间：
2021-01-07
影响因子：
1.6
通讯作者：
Eguchi，Tadashi
中科院分区：
文献类型：
--
作者：
Kudo，Fumitaka;Mori，Ayaka;Eguchi，Tadashi
2-脱氧鲨肌醇（2DOI，[2S，3R，4S，5 R]-2，3，4，5-四羟基环己-1-酮）是一种生物合成的含2-脱氧链霉胺的氨基糖苷类抗生素的中间体，包括布替罗新、卡那霉素和新霉素。在生产微生物中，2DOI由d-葡萄糖6-磷酸（G6 P）通过2-脱氧-鲨肌醇合酶（DOIS）与氧化形式的烟酰胺腺嘌呤二核苷酸（NAD+）构建。2DOI也被认为是生产芳香族化合物和手性环己烷合成子的可持续生物材料。本研究以葡萄糖和多聚磷酸盐为原料，采用酶法一锅法合成2DOI。首先，检测了3种多磷酸葡萄糖激酶（PPGK）从葡萄糖和多磷酸盐产生G6 P。从谷氨酸棒杆菌（Corynebacteriumglutamicum，cgPPGK）中分离得到一种适合于在普通酶促条件下生产G6 P的PPGK。接下来，针对一锅酶促反应检查7个DOIS。结果，cgPPGK和BtrC（后者是来自丁酰松香生产者环状芽孢杆菌的DOI）在多磷酸盐的存在下几乎完全将d-葡萄糖转化为2DOI。
2-Deoxy-scyllo-inosose (2DOI, [2S,3R,4S,5R]-2,3,4,5-tetrahydroxycyclohexan-1-one) is a biosynthetic intermediate of 2-deoxystreptamine-containing aminoglycoside antibiotics, including butirosin, kanamycin, and neomycin. In producer microorganisms, 2DOI is constructed fromd-glucose 6-phosphate (G6P) by 2-deoxy-scyllo-inosose synthase (DOIS) with the oxidized form of nicotinamide adenine dinucleotide (NAD+). 2DOI is also known as a sustainable biomaterial for production of aromatic compounds and a chiral cyclohexane synthon. In this study, a one-pot enzymatic synthesis of 2DOI fromd-glucose and polyphosphate was investigated. First, 3 polyphosphate glucokinases (PPGKs) were examined to produce G6P fromd-glucose and polyphosphate. A PPGK derived fromCorynebacterium glutamicum(cgPPGK) was found to be suitable for G6P production under ordinary enzymatic conditions. Next, 7 DOISs were examined for the one-pot enzymatic reaction. As a result,cgPPGK and BtrC, the latter of which is a DOIS derived from the butirosin producerBacillus circulans, achieved nearly full conversion ofd-glucose to 2DOI in the presence of polyphosphate.