Tahira Naz1, Yusuf Nazir1,2, Shaista Nosheen1, Samee Ullah1,3, Hafiy Halim1, Abu Bakr Ahmad Fazili1, Shaoqi Li1, Kiren Mustafa1, Hassan Mohamed1,4, Wu Yang1, Yuanda Song1. 1. Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo 255000, China. 2. Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia. 3. University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore 54000, Pakistan. 4. Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt.
Abstract
Carotenoids produced by microbial sources are of industrial and medicinal importance due to their antioxidant and anticancer properties. In the current study, optimization of β-carotene production in M. circinelloides strain 277.49 was achieved using response surface methodology (RSM). Cerulenin and ketoconazole were used to inhibit fatty acids and the sterol biosynthesis pathway, respectively, in order to enhance β-carotene production by diverting metabolic pool towards the mevalonate pathway. All three variables used in screening experiments were found to be significant for the production of β-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior β-carotene production using central composite design of RSM. Our results found that the synergistic combination of C/N ratios, cerulenin, and ketoconazole at different concentrations affected the β-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10 μg/mL cerulenin, and 150 mg/L ketoconazole, producing maximum β-carotene of 4.26 mg/L (0.43 mg/g) which was 157% greater in comparison to unoptimized medium (1.68 mg/L, 0.17 mg/g). So, it was concluded that metabolic flux had been successfully redirected towards the mevalonate pathway for enhanced β-carotene production in CBS 277.49.
Carotenoids produced by microbial sources are of industrial and medicinal importance due to their antioxidant and antin class="Disease">cancer properties. In the current study, optimization of β-carotene production in M. circinelloides strain 277.49 was achieved using response surface methodology (RSM). Cerulenin and ketoconazole were used to inhibit fatty acids and the sterol biosynthesis pathway, respectively, in order to enhance β-carotene production by diverting metabolic pool towards the mevalonate pathway. All three variables used in screening experiments were found to be significant for the production of β-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior β-carotene production using central composite design of RSM. Our results found that the synergistic combination of C/N ratios, cerulenin, and ketoconazole at different concentrations affected the β-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10 μg/mL cerulenin, and 150 mg/L ketoconazole, producing maximum β-carotene of 4.26 mg/L (0.43 mg/g) which was 157% greater in comparison to unoptimized medium (1.68 mg/L, 0.17 mg/g). So, it was concluded that metabolic flux had been successfully redirected towards the mevalonate pathway for enhanced β-carotene production in CBS 277.49.
Authors: Ganga Rao Davuluri; Ageeth van Tuinen; Paul D Fraser; Alessandro Manfredonia; Robert Newman; Diane Burgess; David A Brummell; Stephen R King; Joe Palys; John Uhlig; Peter M Bramley; Henk M J Pennings; Chris Bowler Journal: Nat Biotechnol Date: 2005-06-12 Impact factor: 54.908
Authors: Shaista Nosheen; Junhuan Yang; Tahira Naz; Yusuf Nazir; Muhammad Ijaz Ahmad; Abu Bakr Ahmad Fazili; Shaoqi Li; Kiren Mustafa; Yuanda Song Journal: Biotechnol Lett Date: 2020-08-18 Impact factor: 2.461