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Cell Chem Biol. 2017 Jul 20;24(7):881-891.e4. doi: 10.1016/j.chembiol.2017.06.008. Epub 2017 Jul 14.

Formation of an Angular Aromatic Polyketide from a Linear Anthrene Precursor via Oxidative Rearrangement.

Author information

1
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P. R. China.
2
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou 510632, P. R. China.
3
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
4
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P. R. China. Electronic address: jiangming9722@sjtu.edu.cn.
5
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P. R. China. Electronic address: linsj@sjtu.edu.cn.
6
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P. R. China. Electronic address: tao_meifeng@sjtu.edu.cn.

Abstract

Bacterial aromatic polyketides are a group of natural products synthesized by polyketide synthases (PKSs) that show diverse structures and biological activities. They are structurally subclassified into linear, angular, and discoid aromatic polyketides, the formation of which is commonly determined by the shaping and folding of the poly-β-keto intermediates under the concerted actions of the minimal PKSs, cyclases and ketoreductases. Murayaquinone, found in several streptomycetes, possesses an unusual tricyclic angular aromatic polyketide core containing a 9,10-phenanthraquinone. In this study, genes essential for murayaquinone biosynthesis were identified, and a linear anthraoxirene intermediate was discovered. A unique biosynthetic model for the angular aromatic polyketide formation was discovered and confirmed through in vivo and in vitro studies. Three oxidoreductases, MrqO3, MrqO6, and MrqO7, were identified to catalyze the conversion of the linear aromatic polyketide intermediate into the final angularly arranged framework, which exemplifies a novel strategy for the biosynthesis of angular aromatic polyketides.

KEYWORDS:

Baeyer-Villiger oxygenase; angular aromatic polyketides; anthracenone epoxide; biosynthetic pathway; murayaquinone; oxidative rearrangement; oxidoreductase

PMID:
28712746
PMCID:
PMC5584589
DOI:
10.1016/j.chembiol.2017.06.008
[Indexed for MEDLINE]
Free PMC Article

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