A hybrid system for the overproduction of complex ergot alkaloid chanoclavine

Yaqing Ma; Juzhang Yan; Lujia Yang; Yongpeng Yao; Luoyi Wang; Shu-Shan Gao; Chengsen Cui

doi:10.3389/fbioe.2022.1095464

A hybrid system for the overproduction of complex ergot alkaloid chanoclavine

Front Bioeng Biotechnol. 2022 Dec 21:10:1095464. doi: 10.3389/fbioe.2022.1095464. eCollection 2022.

Authors

Yaqing Ma^{1

2

3}, Juzhang Yan², Lujia Yang², Yongpeng Yao¹, Luoyi Wang¹, Shu-Shan Gao^{2

4}, Chengsen Cui^{2

4}

Affiliations

¹ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
² Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ National Technology Innovation Center of Synthetic Biology, Tianjin, China.

Abstract

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.

Keywords: Sbio-Csyn system; cell-lysate catalysis; chemical synthesis; ergot alkaloid; whole-cell catalysis.