Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase

Mellein and the related 3,4-dihydroisocoumarins are a family of natural products with interesting biological properties. The mechanisms of dihydroisocoumarin biosynthesis remain largely speculative today. Here we report the synthesis of mellein by a partially reducing iterative polyketide synthase (...

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Main Authors: Sun, Huihua, Ho, Chun Loong, Ding, Feiqing, Soehano, Ishin, Liu, Xue-Wei, Liang, Zhao-Xun
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2013
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Online Access:https://hdl.handle.net/10356/97615
http://hdl.handle.net/10220/11204
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-976152020-03-07T12:18:06Z Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase Sun, Huihua Ho, Chun Loong Ding, Feiqing Soehano, Ishin Liu, Xue-Wei Liang, Zhao-Xun School of Biological Sciences DRNTU::Science::Biological sciences Mellein and the related 3,4-dihydroisocoumarins are a family of natural products with interesting biological properties. The mechanisms of dihydroisocoumarin biosynthesis remain largely speculative today. Here we report the synthesis of mellein by a partially reducing iterative polyketide synthase (PR-PKS) as a pentaketide product. Remarkably, despite the head-to-tail homology shared with several fungal and bacterial PR-PKSs, the mellein synthase exhibits a distinct keto reduction pattern in the synthesis of the pentaketide. We present evidence to show that the ketoreductase (KR) domain alone is able to recognize and differentiate the polyketide intermediates, which provides a mechanistic explanation for the programmed keto reduction in these PR-PKSs. 2013-07-11T06:14:38Z 2019-12-06T19:44:37Z 2013-07-11T06:14:38Z 2019-12-06T19:44:37Z 2012 2012 Journal Article https://hdl.handle.net/10356/97615 http://hdl.handle.net/10220/11204 10.1021/ja304905e en Journal of the American chemical society © 2012 American Chemical Society.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Sun, Huihua
Ho, Chun Loong
Ding, Feiqing
Soehano, Ishin
Liu, Xue-Wei
Liang, Zhao-Xun
Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase
description Mellein and the related 3,4-dihydroisocoumarins are a family of natural products with interesting biological properties. The mechanisms of dihydroisocoumarin biosynthesis remain largely speculative today. Here we report the synthesis of mellein by a partially reducing iterative polyketide synthase (PR-PKS) as a pentaketide product. Remarkably, despite the head-to-tail homology shared with several fungal and bacterial PR-PKSs, the mellein synthase exhibits a distinct keto reduction pattern in the synthesis of the pentaketide. We present evidence to show that the ketoreductase (KR) domain alone is able to recognize and differentiate the polyketide intermediates, which provides a mechanistic explanation for the programmed keto reduction in these PR-PKSs.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Sun, Huihua
Ho, Chun Loong
Ding, Feiqing
Soehano, Ishin
Liu, Xue-Wei
Liang, Zhao-Xun
format Article
author Sun, Huihua
Ho, Chun Loong
Ding, Feiqing
Soehano, Ishin
Liu, Xue-Wei
Liang, Zhao-Xun
author_sort Sun, Huihua
title Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase
title_short Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase
title_full Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase
title_fullStr Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase
title_full_unstemmed Synthesis of (R)-Mellein by a partially reducing iterative polyketide synthase
title_sort synthesis of (r)-mellein by a partially reducing iterative polyketide synthase
publishDate 2013
url https://hdl.handle.net/10356/97615
http://hdl.handle.net/10220/11204
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