Efficient Production Hyperoside from Quercetin in Escherichia coli Through Increasing UDP-Galactose Supply and Recycling

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Efficient Production Hyperoside from Quercetin in Escherichia coli Through Increasing UDP‑Galactose Supply and Recycling of Resting Cell Na Gu1,2   · Cong Qiu1,2   · Linguo Zhao1,2,4   · Lihu Zhang3   · Jianjun Pei1,2,4  Received: 9 June 2020 / Accepted: 28 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract  Hyperoside is used as the standard to assess the quality of Hyperin perforatum L and exhibits many biological properties. To improve the yield of hyperoside in Escherichia coli, four UDP-galactose synthesis pathways were screened and a recombinant strain was reconstructed by using an efficient UDP-galactose generation system coupled with Petunia hybrida glycosyltransferase to biosynthesis hyperoside from quercetin. By adopting the resting cell transformation, maximal hyperoside production of 4574 mg/L and average productivity of 63.5 mg/L/h were achieved after 72 h of biotranformation. Subsequently through recycling of resting cells, average productivity within 72 h reached 126 mg/L/h, which was 100% higher than that in the batch fermentation. Hyperoside production reached equivalent to 18,000 mg/L by recycling seven times of resting cell in 168 h, which was 393% of that in the batch fermentation and the first to reach 10 g per liter scale in E. coli. Therefore, this study provides an efficient method for construction of UDP-galactose synthesis pathway and hyperoside production in E. coli. Graphic Abstract

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1056​2-020-03373​-y) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article

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Keywords  Hyperoside · UDP-galactose synthesis pathway · Resting cell · Biotranformation

1 Introduction Flavonoids are a large class of over 10,000 natural compounds found in various plants. They are of significant interest due to their varied applications in the fields of flavors, agriculture, nutrition, and pharmaceutics [1–4]. In recent years, some special flavonoids have attracted scientific attention because of their effective pharmaceutical activities such as antiviral, anti-inflammatory, antidepressant, apoptotic, and antifungal activities [5–12]. For example, hyperoside (quercetin 3-O-galactoside) is used as the standard to assess the quality of Hyperin perforatum L, which is traditional Chinese medicine and exhibits higher bioactivity compared to that of quercetin in some respects [8, 11]. However, it is difficult to produce hyperoside in an industrial scale because of its low concentration and complex composition in the plants [13, 14]. Quercetin has been cheaply produced in an industrial scale from Sophora japonica L. via solvent extraction, hydrolysis, and column chromatography in China [15]. Hyperoside has one more galactose residue at the C-3 position than quercetin. Theoretically, hyperoside can be obtained by glycosylating quercetin at the C-3 position [16