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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797979688686059520 |
---|---|
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. |
first_indexed | 2024-04-11T05:43:52Z |
format | Article |
id | doaj.art-bf4b1ddba8ad4fdf8e8180be16ba513f |
institution | Directory Open Access Journal |
issn | 2296-4185 |
language | English |
last_indexed | 2024-04-11T05:43:52Z |
publishDate | 2022-12-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Bioengineering and Biotechnology |
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 |
work_keys_str_mv | AT yaqingma ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yaqingma ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yaqingma ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT juzhangyan ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT lujiayang ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yongpengyao ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT luoyiwang ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT shushangao ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT shushangao ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT chengsencui ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT chengsencui ahybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yaqingma hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yaqingma hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yaqingma hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT juzhangyan hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT lujiayang hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT yongpengyao hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT luoyiwang hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT shushangao hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT shushangao hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT chengsencui hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine AT chengsencui hybridsystemfortheoverproductionofcomplexergotalkaloidchanoclavine |