Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition

Abstract Oxygen limitation is regarded as a useful strategy to improve enzyme production by mycelial fungus like Aspergillus niger. However, the intracellular metabolic response of A. niger to oxygen limitation is still obscure. To address this, the metabolism of A. niger was studied using multi-omi...

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Autores principales:	Hongzhong Lu, Weiqiang Cao, Xiaoyun Liu, Yufei Sui, Liming Ouyang, Jianye Xia, Mingzhi Huang, Yingping Zhuang, Siliang Zhang, Henk Noorman, Ju Chu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Integrative Multi-omics Analysis Genome-scale Metabolic Model (GEMs) Oxygen-limited Phase Supplementary File Simulated Fluxes Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2275fea23044cf8837565ad61a4610a
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spelling	oai:doaj.org-article:d2275fea23044cf8837565ad61a4610a2021-12-02T11:40:55ZMulti-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition10.1038/s41598-018-32341-12045-2322https://doaj.org/article/d2275fea23044cf8837565ad61a4610a2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32341-1https://doaj.org/toc/2045-2322Abstract Oxygen limitation is regarded as a useful strategy to improve enzyme production by mycelial fungus like Aspergillus niger. However, the intracellular metabolic response of A. niger to oxygen limitation is still obscure. To address this, the metabolism of A. niger was studied using multi-omics integrated analysis based on the latest GEMs (genome-scale metabolic model), including metabolomics, fluxomics and transcriptomics. Upon sharp reduction of the oxygen supply, A. niger metabolism shifted to higher redox level status, as well as lower energy supply, down-regulation of genes for fatty acid synthesis and a rapid decrease of the specific growth rate. The gene expression of the glyoxylate bypass was activated, which was consistent with flux analysis using the A. niger GEMs iHL1210. The increasing flux of the glyoxylate bypass was assumed to reduce the NADH formation from TCA cycle and benefit maintenance of the cellular redox balance under hypoxic conditions. In addition, the relative fluxes of the EMP pathway were increased, which possibly relieved the energy demand for cell metabolism. The above multi-omics integrative analysis provided new insights on metabolic regulatory mechanisms of A. niger associated with enzyme production under oxygen-limited condition, which will benefit systematic design and optimization of the A. niger microbial cell factory.Hongzhong LuWeiqiang CaoXiaoyun LiuYufei SuiLiming OuyangJianye XiaMingzhi HuangYingping ZhuangSiliang ZhangHenk NoormanJu ChuNature PortfolioarticleIntegrative Multi-omics AnalysisGenome-scale Metabolic Model (GEMs)Oxygen-limited PhaseSupplementary FileSimulated FluxesMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Integrative Multi-omics Analysis Genome-scale Metabolic Model (GEMs) Oxygen-limited Phase Supplementary File Simulated Fluxes Medicine R Science Q
spellingShingle	Integrative Multi-omics Analysis Genome-scale Metabolic Model (GEMs) Oxygen-limited Phase Supplementary File Simulated Fluxes Medicine R Science Q Hongzhong Lu Weiqiang Cao Xiaoyun Liu Yufei Sui Liming Ouyang Jianye Xia Mingzhi Huang Yingping Zhuang Siliang Zhang Henk Noorman Ju Chu Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
description	Abstract Oxygen limitation is regarded as a useful strategy to improve enzyme production by mycelial fungus like Aspergillus niger. However, the intracellular metabolic response of A. niger to oxygen limitation is still obscure. To address this, the metabolism of A. niger was studied using multi-omics integrated analysis based on the latest GEMs (genome-scale metabolic model), including metabolomics, fluxomics and transcriptomics. Upon sharp reduction of the oxygen supply, A. niger metabolism shifted to higher redox level status, as well as lower energy supply, down-regulation of genes for fatty acid synthesis and a rapid decrease of the specific growth rate. The gene expression of the glyoxylate bypass was activated, which was consistent with flux analysis using the A. niger GEMs iHL1210. The increasing flux of the glyoxylate bypass was assumed to reduce the NADH formation from TCA cycle and benefit maintenance of the cellular redox balance under hypoxic conditions. In addition, the relative fluxes of the EMP pathway were increased, which possibly relieved the energy demand for cell metabolism. The above multi-omics integrative analysis provided new insights on metabolic regulatory mechanisms of A. niger associated with enzyme production under oxygen-limited condition, which will benefit systematic design and optimization of the A. niger microbial cell factory.
format	article
author	Hongzhong Lu Weiqiang Cao Xiaoyun Liu Yufei Sui Liming Ouyang Jianye Xia Mingzhi Huang Yingping Zhuang Siliang Zhang Henk Noorman Ju Chu
author_facet	Hongzhong Lu Weiqiang Cao Xiaoyun Liu Yufei Sui Liming Ouyang Jianye Xia Mingzhi Huang Yingping Zhuang Siliang Zhang Henk Noorman Ju Chu
author_sort	Hongzhong Lu
title	Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
title_short	Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
title_full	Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
title_fullStr	Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
title_full_unstemmed	Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition
title_sort	multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of aspergillus niger under industrial enzyme production condition
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d2275fea23044cf8837565ad61a4610a
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Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition

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