Enhanced Production of Androst-1,4-Diene-3,17-Dione by Mycobacterium neoaurum JC-12 Using Three-Stage Fermentation Strategy.
To improve the androst-1,4-diene-3,17-dione (ADD) production from phytosterol by Mycobacterium neoaurum JC-12, fructose was firstly found favorable as the initial carbon source to increase the biomass and eliminate the lag phase of M. neoaurum JC-12 in the phytosterol transformation process. Based on this phenomenon, two-stage fermentation by using fructose as the initial carbon source and feeding glucose to maintain strain metabolism was designed. By applying this strategy, the fermentation duration was decreased from 168 h to 120 h with the ADD productivity increased from 0.071 g/(L·h) to 0.108 g/(L·h). Further, three-stage fermentation by adding phytosterol to improve ADD production at the end of the two-stage fermentation was carried out and the final ADD production reached 18.6 g/L, which is the highest reported ADD production using phytosterol as substrate. Thus, this strategy provides a possible way in enhancing the ADD production in pharmaceutical industry.
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Laboratory of Applied Microorganisms and Metabolic Engineering, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Minglong
M
Shao
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Laboratory of Applied Microorganisms and Metabolic Engineering, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Xian
X
Zhang
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Laboratory of Applied Microorganisms and Metabolic Engineering, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Zhiming
Z
Rao
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Laboratory of Applied Microorganisms and Metabolic Engineering, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Meijuan
M
Xu
The Key Laboratory of Industrial Biotechnology, Ministry of Education, Laboratory of Applied Microorganisms and Metabolic Engineering, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Taowei
T
Yang
Laboratory of Pharmaceutical Engineering, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Hui
H
Li
Laboratory of Pharmaceutical Engineering, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
Zhenghong
Z
Xu
D000730:Androstadienes / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D005285:Fermentation; D005632:Fructose / Q000737:chemistry / Q000378:metabolism; D009161:Mycobacterium / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D010840:Phytosterols / Q000096:biosynthesis* / Q000737:chemistry; D011090:Polyenes / Q000737:chemistry
D000730:Androstadienes; D010840:Phytosterols; D011090:Polyenes; C006573:1,4-androstadiene-3,17-dione; D005632:Fructose; D002244:Carbon; D010088:Oxidoreductases