Biosynthetic access to the rare antiarose sugar via an unusual reductase-epimerase

Yijun Yan; Jing Yang; Li Wang; Dongdong Xu; Zhiyin Yu; Xiaowei Guo; Geoff P. Horsman; Shuangjun Lin; Meifeng Tao; Sheng-Xiong Huang

doi:10.1039/C9SC05766H

Biosynthetic access to the rare antiarose sugar via an unusual reductase-epimerase†

Yijun Yan,

‡^a Jing Yang,‡^a Li Wang,

‡^a Dongdong Xu,^a Zhiyin Yu,^a Xiaowei Guo,^a Geoff P. Horsman,^c Shuangjun Lin,

^b Meifeng Tao^b and Sheng-Xiong Huang

*^a

Author affiliations

* Corresponding authors

^a State Key Laboratory of Phytochemistry and Plant Resources in West China, CAS Center for Excellence in Molecular Plant Sciences, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
E-mail: sxhuang@mail.kib.ac.cn

^b State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China

^c Department of Chemistry & Biochemistry, Wilfrid Laurier University, Waterloo, ON N2L 3C5, Canada

Abstract

Rubrolones, isatropolones, and rubterolones are recently isolated glycosylated tropolonids with notable biological activity. They share similar aglycone skeletons but differ in their sugar moieties, and rubterolones in particular have a rare deoxysugar antiarose of unknown biosynthetic provenance. During our previously reported biosynthetic elucidation of the tropolone ring and pyridine moiety, gene inactivation experiments revealed that RubS3 is involved in sugar moiety biosynthesis. Here we report the in vitro characterization of RubS3 as a bifunctional reductase/epimerase catalyzing the formation of TDP-D-antiarose by epimerization at C3 and reduction at C4 of the key intermediate TDP-4-keto-6-deoxy-D-glucose. These new findings not only explain the biosynthetic pathway of deoxysugars in rubrolone-like natural products, but also introduce RubS3 as a new family of reductase/epimerase enzymes with potential to supply the rare antiarose unit for expanding the chemical space of glycosylated natural products.

Chemical Science

Biosynthetic access to the rare antiarose sugar via an unusual reductase-epimerase†

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Biosynthetic access to the rare antiarose sugar via an unusual reductase-epimerase

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