A hybrid system for the overproduction of complex ergot alkaloid chanoclavine

Synthetic biology-based methods (Sbio) and chemical synthesis (Csyn) are two independent approaches that are both widely used for synthesizing biomolecules. In the current study, two systems were combined for the overproduction of chanoclavine (CC), a structurally complex ergot alkaloid. The whole s...

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Main Authors: Yaqing Ma, Juzhang Yan, Lujia Yang, Yongpeng Yao, Luoyi Wang, Shu-Shan Gao, Chengsen Cui
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.1095464/full
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author Yaqing Ma
Yaqing Ma
Yaqing Ma
Juzhang Yan
Lujia Yang
Yongpeng Yao
Luoyi Wang
Shu-Shan Gao
Shu-Shan Gao
Chengsen Cui
Chengsen Cui
author_facet Yaqing Ma
Yaqing Ma
Yaqing Ma
Juzhang Yan
Lujia Yang
Yongpeng Yao
Luoyi Wang
Shu-Shan Gao
Shu-Shan Gao
Chengsen Cui
Chengsen Cui
author_sort Yaqing Ma
collection DOAJ
description Synthetic biology-based methods (Sbio) and chemical synthesis (Csyn) are two independent approaches that are both widely used for synthesizing biomolecules. In the current study, two systems were combined for the overproduction of chanoclavine (CC), a structurally complex ergot alkaloid. The whole synthetic pathway for CC was split into three sections: enzymatic synthesis of 4-Br-Trp (4-Bromo-trptophan) using cell-lysate catalysis (CLC), chemical synthesis of prechanoclavine (PCC) from 4-Br-Trp, and overproduction CC from PCC using a whole-cell catalysis (WCC) platform. The final titer of the CC is over 3 g/L in this Sbio-Csyn hybrid system, the highest yield reported so far, to the best of our knowledge. The development of such a combined route could potentially avoid the limitations of both Sbio and Csyn systems and boost the overproduction of complex natural products.
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spelling doaj.art-bf4b1ddba8ad4fdf8e8180be16ba513f2022-12-22T04:42:20ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-12-011010.3389/fbioe.2022.10954641095464A hybrid system for the overproduction of complex ergot alkaloid chanoclavineYaqing Ma0Yaqing Ma1Yaqing Ma2Juzhang Yan3Lujia Yang4Yongpeng Yao5Luoyi Wang6Shu-Shan Gao7Shu-Shan Gao8Chengsen Cui9Chengsen Cui10CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaNational Technology Innovation Center of Synthetic Biology, Tianjin, ChinaTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, ChinaNational Technology Innovation Center of Synthetic Biology, Tianjin, ChinaSynthetic biology-based methods (Sbio) and chemical synthesis (Csyn) are two independent approaches that are both widely used for synthesizing biomolecules. In the current study, two systems were combined for the overproduction of chanoclavine (CC), a structurally complex ergot alkaloid. The whole synthetic pathway for CC was split into three sections: enzymatic synthesis of 4-Br-Trp (4-Bromo-trptophan) using cell-lysate catalysis (CLC), chemical synthesis of prechanoclavine (PCC) from 4-Br-Trp, and overproduction CC from PCC using a whole-cell catalysis (WCC) platform. The final titer of the CC is over 3 g/L in this Sbio-Csyn hybrid system, the highest yield reported so far, to the best of our knowledge. The development of such a combined route could potentially avoid the limitations of both Sbio and Csyn systems and boost the overproduction of complex natural products.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1095464/fullergot alkaloidcell-lysate catalysischemical synthesiswhole-cell catalysisSbio-Csyn system
spellingShingle Yaqing Ma
Yaqing Ma
Yaqing Ma
Juzhang Yan
Lujia Yang
Yongpeng Yao
Luoyi Wang
Shu-Shan Gao
Shu-Shan Gao
Chengsen Cui
Chengsen Cui
A hybrid system for the overproduction of complex ergot alkaloid chanoclavine
Frontiers in Bioengineering and Biotechnology
ergot alkaloid
cell-lysate catalysis
chemical synthesis
whole-cell catalysis
Sbio-Csyn system
title A hybrid system for the overproduction of complex ergot alkaloid chanoclavine
title_full A hybrid system for the overproduction of complex ergot alkaloid chanoclavine
title_fullStr A hybrid system for the overproduction of complex ergot alkaloid chanoclavine
title_full_unstemmed A hybrid system for the overproduction of complex ergot alkaloid chanoclavine
title_short A hybrid system for the overproduction of complex ergot alkaloid chanoclavine
title_sort hybrid system for the overproduction of complex ergot alkaloid chanoclavine
topic ergot alkaloid
cell-lysate catalysis
chemical synthesis
whole-cell catalysis
Sbio-Csyn system
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.1095464/full
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