Combined dissolved oxygen and pH control strategy to improve the fermentative production of l-isoleucine by Brevibacterium lactofermentum

Peng, Zhijian; Fang, Jun; Li, Jianghua; Liu, Long; Du, Guocheng; Chen, Jian; Wang, Xiaoyuan; Ning, Jianfei; Cai, Liming

doi:10.1007/s00449-009-0329-6

Cited by 13 publications

(2 citation statements)

References 15 publications

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“…pH and agitation speed were controlled at 6.7 and 800 rpm, respectively, until 12 h, after which an agitation speed of 600 rpm and a pH 7.2 were applied. Using this two-stage pH and DO control strategy, 27.3% increase in L-isoleucine production (26.6 g/L from 140 g/L glucose) was achieved [95]. In another study, the E. coli catabolic threonine dehydratase (encoded by tdcB) was found to be more beneficial for enhanced production of L-isoleucine in C. glutamicum upon overexpression than C. glutamicum threonine dehydratase (encoded by ilvA).…”

Section: L-isoleucine Production Strainsmentioning

confidence: 98%

Metabolic pathways and fermentative production of L‐aspartate family amino acids

Park

Lee

2010

Biotechnology Journal

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The L-aspartate family amino acids (AFAAs), L-threonine, L-lysine, L-methionine and L-isoleucine have recently been of much interest due to their wide spectrum of applications including food additives, components of cosmetics and therapeutic agents, and animal feed additives. Among them, L-threonine, L-lysine and L-methionine are three major amino acids produced currently throughout the world. Recent advances in systems metabolic engineering, which combine various high-throughput omics technologies and computational analysis, are now facilitating development of microbial strains efficiently producing AFAAs. Thus, a thorough understanding of the metabolic and regulatory mechanisms of the biosynthesis of these amino acids is urgently needed for designing system-wide metabolic engineering strategies. Here we review the details of AFAA biosynthetic pathways, regulations involved, and export and transport systems, and provide general strategies for successful metabolic engineering along with relevant examples. Finally, perspectives of systems metabolic engineering for developing AFAA overproducers are suggested with selected exemplary studies.

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Section: L-isoleucine Production Strainsmentioning

confidence: 98%

Metabolic pathways and fermentative production of L‐aspartate family amino acids

Park

Lee

2010

Biotechnology Journal

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“…Oxygen limitation changes the redox state of microbial cells [ 12 , 28 ]. For the production of aromatic compounds, the DO level is generally controlled at ≥ 20% of saturated oxygen, such as the production of phenylalanine (Phe) [ 29 ] by C. glutamicum and the production of tryptophan (Trp) [ 30 ], shikimate [ 19 ], and Tyr [ 31 ] by E. coli .…”

Section: Discussionmentioning

confidence: 99%

Enhanced production of γ-amino acid 3-amino-4-hydroxybenzoic acid by recombinant Corynebacterium glutamicum under oxygen limitation

et al. 2021

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Background Bio-based aromatic compounds are of great interest to the industry, as commercial production of aromatic compounds depends exclusively on the unsustainable use of fossil resources or extraction from plant resources. γ-amino acid 3-amino-4-hydroxybenzoic acid (3,4-AHBA) serves as a precursor for thermostable bioplastics. Results Under aerobic conditions, a recombinant Corynebacterium glutamicum strain KT01 expressing griH and griI genes derived from Streptomyces griseus produced 3,4-AHBA with large amounts of amino acids as by-products. The specific productivity of 3,4-AHBA increased with decreasing levels of dissolved oxygen (DO) and was eightfold higher under oxygen limitation (DO = 0 ppm) than under aerobic conditions (DO ≥ 2.6 ppm). Metabolic profiles during 3,4-AHBA production were compared at three different DO levels (0, 2.6, and 5.3 ppm) using the DO-stat method. Results of the metabolome analysis revealed metabolic shifts in both the central metabolic pathway and amino acid metabolism at a DO of < 33% saturated oxygen. Based on this metabolome analysis, metabolic pathways were rationally designed for oxygen limitation. An ldh deletion mutant, with the loss of lactate dehydrogenase, exhibited 3.7-fold higher specific productivity of 3,4-AHBA at DO = 0 ppm as compared to the parent strain KT01 and produced 5.6 g/L 3,4-AHBA in a glucose fed-batch culture. Conclusions Our results revealed changes in the metabolic state in response to DO concentration and provided insights into oxygen supply during fermentation and the rational design of metabolic pathways for improved production of related amino acids and their derivatives. Graphical Abstract

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Engineering Brevibacterium flavum for the production of renewable bioenergy: C4–C5 advanced alcohols

Lin

Qiao

et al. 2017

Biotech & Bioengineering

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Biosynthesis of advanced biofuels by engineered non-natural microorganisms has been proposed to be the most promising approach for the replacement of dwindling fossil fuel resources. Brevibacterium flavum (Bf) is a model brevibacterium aerobe which lacks basic and applied research that could enable this species to produce biofuels. There are no reports regarding engineering this microorganism to produce advanced alcohols before. Here, for the first time, we developed the bacterium as a novel biosynthetic platform for advanced alcohols production via the mutagenesis and engineering to produce 2-ketoacids derived alcohols. In order to enhance the strain's capability of producing advanced alcohols, we preferentially improved intrinsic metabolism ability of the strain to obtain improved expression host (IEH) via generating mutagenesis libraries by whole cell mutagenesis (WCM). The IEH was determined via screening out the mutant strain with the highest production of branched-chain organic acids (BCOA) using high throughput screening method.. Subsequently, a novel vector system for Bf was established, and the corresponding biosynthetic pathway of directing carbon flux into the target advanced alcohols was recruited to make the bacterium possess the capability of producing advanced alcohols and further enhance the production using the IEH. Specifically, we generated bioengineered strains that were able to synthesize up to the highest 5362 and 4976 mg/L isobutanol, 1945 and 1747 mg/L 2-methyl-1-butanol (2 MB), and 785.34 and 781 mg/L 3-methyl-1-butanol (3 MB) from pure glucose and duckweed substrates, respectively. Our findings confirmed the feasibility and potential of using Bf as a novel biosynthetic platform to generate advanced biofuels with glucose and inexpensive renewable feedstock-duckweed as a fermentation substrate. Biotechnol. Bioeng. 2017;114: 1946-1958. © 2017 Wiley Periodicals, Inc.

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Combined dissolved oxygen and pH control strategy to improve the fermentative production of l-isoleucine by Brevibacterium lactofermentum

Cited by 13 publications

References 15 publications

Metabolic pathways and fermentative production of L‐aspartate family amino acids

Metabolic pathways and fermentative production of L‐aspartate family amino acids

Enhanced production of γ-amino acid 3-amino-4-hydroxybenzoic acid by recombinant Corynebacterium glutamicum under oxygen limitation

Engineering Brevibacterium flavum for the production of renewable bioenergy: C4–C5 advanced alcohols

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