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Integration of Parallel

Haishan Qi, Mengmeng Lv, Kejing Song, Jianping Wen

Biotechnol Bioeng. 2017 May;114(5):1036-1044.

PMID: 27869289

Abstract:

Herein, the hyper-producing strain for ascomycin was engineered based on 13 C-labeling experiments and elementary flux modes analysis (EFMA). First, the metabolism of non-model organism Streptomyces hygroscopicus var. ascomyceticus SA68 was investigated and an updated network model was reconstructed using 13 C- metabolic flux analysis. Based on the precise model, EFMA was further employed to predict genetic targets for higher ascomycin production. Chorismatase (FkbO) and pyruvate carboxylase (Pyc) were predicted as the promising overexpression and deletion targets, respectively. The corresponding mutant TD-FkbO and TD-ΔPyc exhibited the consistency effects between model prediction and experimental results. Finally, the combined genetic manipulations were performed, achieving a high-yield ascomycin engineering strain TD-ΔPyc-FkbO with production up to 610 mg/L, 84.8% improvement compared with the parent strain SA68. These results manifested that the integration of 13 C-labeling experiments and in silico pathway analysis could serve as a promising concept to enhance ascomycin production, as well as other valuable products. Biotechnol. Bioeng. 2017;114: 1036-1044. © 2016 Wiley Periodicals, Inc.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP104987124-B Ascomycin from Streptomyces hygroscopicus var. ascomyceticus Ascomycin from Streptomyces hygroscopicus var. ascomyceticus 104987-12-4 Price
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