期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 69, 期 44, 页码 13135-13142出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c05486
关键词
alpha-santalene; indole; RBS manipulation; metabolic engineering; Escherichia coli
资金
- National Natural Science Foundation of China [21878198]
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [2021R1A5A8029490]
- Undergraduate Training Program for Innovation and Entrepreneurship [2019XJ073]
- Soochow University
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Suzhou Municipal Science and Technology Bureau [SNG201916]
- National Research Foundation of Korea [2021R1A5A8029490] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This study optimized an alpha-santalene synthetic operon in E. coli by manipulating ribosome binding sites (RBSs). Deletion of the tnaA gene led to an increase in alpha-santalene production. These results suggest that optimizing the RBS sets of the synthetic module and attenuating competitive pathways are promising approaches for improving terpenoid production.
alpha-Santalene belongs to a class of natural compounds with many physiological functions and medical applications. Advances in metabolic engineering enable non-native hosts (e.g., Escherichia coli) to produce alpha-santalene, the precursor of sandalwood oil. However, imbalances in enzymatic activity often result in a metabolic burden on hosts and repress the synthetic capacity of the desired product. In this work, we manipulated ribosome binding sites (RBSs) to optimize an alpha-santalene synthetic operon in E. coli, and the best engineered E. coli NA-IS3D strain could produce alpha-santalene at a titer of 412 mg.L-1. Concerning the observation of the inverse correlation between indole synthesis and alpha-santalene production, this study speculated that indoleassociated amino acid metabolism would be competitive to the synthesis of alpha-santalene rather than indole toxicity itself. The deletion of tnaA could lead to a 1.5-fold increase in alpha-santalene production to a titer of 599 mg.L-1 in E. coli tnaA(-) NA-IS3D. Our results suggested that the optimization of RBS sets of the synthetic module and attenuation of the competitive pathway are promising approaches for improving the production of terpenoids including alpha-santalene.
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