Dataset Information

Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced ?-Carotene Production in M. circinelloides CBS 277.49.

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 ?-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 ?-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 ?-carotene. The synergistic effect of the C/N ratio, cerulenin, and ketoconazole was further evaluated and optimized for superior ?-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 ?-carotene productions significantly. The optimal production medium (std. order 11) composed of C/N 25, 10??g/mL cerulenin, and 150?mg/L ketoconazole, producing maximum ?-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 ?-carotene production in CBS 277.49.

SUBMITTER: Naz T

PROVIDER: S-EPMC7785371 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced β-Carotene Production in M. circinelloides CBS 277.49.

Naz Tahira T Nazir Yusuf Y Nosheen Shaista S Ullah Samee S Halim Hafiy H Fazili Abu Bakr Ahmad ABA Li Shaoqi S Mustafa Kiren K Mohamed Hassan H Yang Wu W Song Yuanda Y

BioMed research international 20201229

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 ...[more]

PMID: 33457420

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Project description:BACKGROUND:Mitochondrial and cytoplasmic malate transporter proteins are responsible for transmembrane transport of malate, thereby linking malate metabolism in various subcellular regions of the cell. These transporters play an important role in fatty acid biosynthesis of oleaginous microorganisms. Our previous studies have found that lipid content of the recombinant Mucor circinelloides (M. circinelloides) strain with mitochondrial malate transporter (mt) gene overexpression was increased by 70%, while that of strain with mt gene knockout was decreased by 27%. However, the mechanism of malate transporter promoting the transport of mitochondrial malate and citrate related to lipid accumulation is not clear. Therefore, 13C-labeled glucose metabolic flux analysis was carried out to identify the metabolic network topology and estimate intracellular fluxes of genetically engineered M. circinelloides strains for the purpose of better understanding the roles of malate transporters in citrate transport systems and lipid accumulation. RESULTS:The metabolic flux distribution analysis suggested that tricarboxylic acid (TCA) cycle flux ratio of mt-overexpression strains was decreased compared to that of the control strain, but in contrast, glyoxylic acid (GOX) cycle flux ratio was increased. Accordingly, the mt-knockout strain showed an opposite phenomenon with a higher TCA cycle flux ratio and a lower GOX cycle flux ratio than the control strain. GOX cycle might be more effective than TCA cycle in producing malate and oxaloacetate replenishment. Moreover, a relatively higher flux ratio of the pentose phosphate (PP) pathway was obtained in mt-overexpression strains, but no significant difference in the malic enzyme flux between recombinant strains and the control strain. Our results confirmed that PP pathway might play an important role for supplying NADPH and malic enzyme is not a limiting factor for fatty acid synthesis in oleaginous fungus M. circinelloides strains. CONCLUSION:Intracellular metabolic flux information suggested that mt-overexpression strains had higher flux in PP pathway and GOX cycle, lower flux in TCA cycle, and no difference in malic enzyme cycle. Together, the role of malate transporter was assumed to further participate in transporting cycle of acetyl-CoA and drive PP pathway to supply NADPH required for lipid accumulation in recombinant M. circinelloides strains.

Dataset Information

Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced ?-Carotene Production in M. circinelloides CBS 277.49.

Publications

Redirecting Metabolic Flux towards the Mevalonate Pathway for Enhanced <i>β</i>-Carotene Production in <i>M. circinelloides</i> CBS 277.49.

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