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A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases |
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| Authors: | Haoyu Liang Lin Jiang Qiyun Jiang Jie Shi Jingxi Xiang Xiaohui Yan Xiangcheng Zhu Lixing Zhao Ben Shen Yanwen Duan Yong Huang |
| Institution: | 1. School of Geosciences and Info-physics at Central South University, Changsha, Hunan, China;2. Xiangya International Academy of Translational Medicine at Central South University, Changsha, Hunan, China;3. Xiangya International Academy of Translational Medicine at Central South University, Changsha, Hunan, China
National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, Hunan, China;4. Xiangya International Academy of Translational Medicine at Central South University, Changsha, Hunan, China National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, Hunan, China Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, Hunan, China;5. Yunnan Institute of Microbiology, Yunnan University, Kunming, Yunnan, China;6. Department of Chemistry, The Scripps Research Institute, Jupiter, FL, USA Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA Natural Products Library Initiative at The Scripps Research Institute, The Scripps Research Institute, Jupiter, FL, USA |
| Abstract: | Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for β-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs through in silico genome mining, sequence and genome neighbourhood network analyses. Using HCS-based probes, the survey of 1207 in-house strains and 18 soil samples from different geographic locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. This study provides a new probe to study the abundance and diversity of AT-less type I PKSs in the environment and microbial strain collections. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs. |
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