PNAS
Abstract
Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hop (Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two non-catalytic chalcone isomerase-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase (PT), and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a novel function of HlCHIL1 to bind DMX and naringenin chalcone (NC) to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis in hops, and provides insight into their evolutionary development from the ancestral fatty acid-binding CHI-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants.
| 论文编号: | DOI:10.1073/pnas.1802223115 |
| 论文题目: | Noncatalytic Chalcone Isomerase-fold Proteins in Humulus lupulus Are Auxiliary Components in Prenylated Flavonoid Biosynthesis |
| 英文论文题目: | Noncatalytic Chalcone Isomerase-fold Proteins in Humulus lupulus Are Auxiliary Components in Prenylated Flavonoid Biosynthesis |
| 第一作者: | Zhaonan Ban, Hao Qin, Andrew J. Mitchell, Baoxiu Liu, Fengxia Zhang, Jing-Ke Weng, Richard A. Dixon, and Guodong Wang |
| 英文第一作者: | Zhaonan Ban, Hao Qin, Andrew J. Mitchell, Baoxiu Liu, Fengxia Zhang, Jing-Ke Weng, Richard A. Dixon, and Guodong Wang |
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| 发表年度: | 2018-05-15 |
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| 摘要: | Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hop (Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two non-catalytic chalcone isomerase-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase (PT), and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a novel function of HlCHIL1 to bind DMX and naringenin chalcone (NC) to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis in hops, and provides insight into their evolutionary development from the ancestral fatty acid-binding CHI-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants. |
| 英文摘要: | Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hop (Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two non-catalytic chalcone isomerase-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase (PT), and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a novel function of HlCHIL1 to bind DMX and naringenin chalcone (NC) to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis in hops, and provides insight into their evolutionary development from the ancestral fatty acid-binding CHI-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants. |
| 刊物名称: | PNAS |
| 英文刊物名称: | PNAS |
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| 其它备注: | Zhaonan Ban, Hao Qin, Andrew J. Mitchell, Baoxiu Liu, Fengxia Zhang, Jing-Ke Weng, Richard A. Dixon, and Guodong Wang. Noncatalytic Chalcone Isomerase-fold Proteins in Humulus lupulus Are Auxiliary Components in Prenylated Flavonoid Biosynthesis. PNAS. DOI:10.1073/pnas.1802223115 |
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