BACKGROUND Type III polyketide synthases (PKSs) contribute to the synthesis of many economically important natural products, which are typically produced by direct extraction from plants or synthesized chemically. For example, humulone and lupulone (Fig. 1a) in hops (Humulus lupulus) account for the characteristic bitter taste of beer and display multiple pharmacological effects. 4-Hydroxy-6-methyl-2-pyrone is a precursor of parasorboside contributing to insect and disease resistance of plant Gerbera hybrida, and was recently demonstrated to be a potential platform chemical. Fig. 1 Examples of phloroglucinols (a) and 2-pyrones (b) synthesized by type III PKS. PIBP phlorisobutyrophenone; PIVP phlorisovalerophenone; TAL 4-hydroxy-6-methyl-2-pyrone (triacetic acid lactone); HIPP 4-hydroxy-6-isopropyl-2-pyrone; HIBP 4-hydroxy-6-isobutyl-2-pyrone RESULTS In this study, we achieved simultaneous biosynthesis of phlorisovalerophenone, a key intermediate of humulone biosynthesis and 4-hydroxy-6-isobutyl-2-pyrone in Escherichia coli from glucose. First, we constructed a biosynthetic pathway of isovaleryl-CoA via hydroxy-3-methylglutaryl CoA followed by dehydration, decarboxylation and reduction in E. coli. Subsequently, the type III PKSs valerophenone synthase or chalcone synthase from plants were introduced into the above E. coli strain, to produce phlorisovalerophenone and 4-hydroxy-6-isobutyl-2-pyrone at the highest titers of 6.4 or 66.5 mg/L, respectively. CONCLUSIONS The report of biosynthesis of phlorisovalerophenone and 4-hydroxy-6-isobutyl-2-pyrone in E. coli adds a new example to the list of valuable compounds synthesized in E. coli from renewable carbon resources by type III PKSs.

中文翻译：

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由葡萄糖在大肠杆菌中生物合成间苯二异戊酮和4-羟基-6-异丁基-2-吡喃酮。

背景技术III型聚酮化合物合酶（PKS）有助于许多经济上重要的天然产物的合成，这些产物通常是通过直接从植物中提取或化学合成而制备的。例如，啤酒花（Humulus lupulus）中的草酮和羽扇豆（图1a）说明了啤酒的苦味特征，并表现出多种药理作用。4-羟基-6-甲基-2-吡喃酮是山梨糖苷的前体，有助于植物非洲菊杂种的抗虫和抗病性，最近被证明是一种潜在的平台化学品。图1通过III型PKS合成的间苯三酚（a）和2-吡喃酮（b）的实例。PIBP氯异丁酮 PIVP苯异戊二酮; TAL 4-羟基-6-甲基-2-吡喃酮（三乙酸内酯）; HIPP 4-羟基-6-异丙基-2-吡喃酮; HIBP 4-羟基-6-异丁基-2-吡喃酮结果在这项研究中，我们从葡萄糖中同时实现了枯草酮生物合成的关键中间体苯并异戊二酮和4-羟基-6-异丁基-2-吡喃酮的生物合成。首先，我们通过羟基-3-甲基戊二酰辅酶A，然后在大肠杆菌中进行脱水，脱羧和还原，构建了异戊酰-CoA的生物合成途径。随后，将来自植物的III型PKSs戊苯酮合酶或查尔酮合酶引入上述大肠杆菌菌株中，以最高滴度为6.4或66.5 mg / L产生苯异戊二酮和4-羟基-6-异丁基-2-吡喃酮，分别。结论在大肠杆菌中生物合成间苯二异戊酮和4-羟基-6-异丁基-2-吡喃酮的报道为在大肠杆菌中合成的有价值的化合物清单增加了新的例子。