Lysine overproducing Corynebacterium glutamicum is characterized by a robust linear combination of two optimal phenotypic states

Rajvanshi, Meghna; Gayen, Kalyan; Venkatesh, K. V.

doi:10.1007/s11693-013-9107-5

Cited by 4 publications

(2 citation statements)

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“…A great deal of work has been conducted to elucidate the complex catabolism of lysine in P. putida (Thompson et al., 2019a, Zhang et al., 2018), yet relatively little work has been done to increase flux to lysine within the bacterium. While there has been little to divert flux to L-lysine in P. putida , there is a wealth of evidence in other bacteria where high titers of intracellular lysine have been achieved (Nærdal et al., 2011, Rajvanshi et al., 2013). The ever increasing body of research to characterize the sprawling metabolism of P. putida will greatly aid in future efforts of efficient production of valerolactam from lignocellulosic feedstocks.…”

Section: Discussionmentioning

confidence: 99%

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer

Thompson

Valencia

Blake-Hedges

et al. 2019

Metabolic Engineering Communications

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Pseudomonas putida is a promising bacterial chassis for metabolic engineering given its ability to metabolize a wide array of carbon sources, especially aromatic compounds derived from lignin. However, this omnivorous metabolism can also be a hindrance when it can naturally metabolize products produced from engineered pathways. Herein we show that P. putida is able to use valerolactam as a sole carbon source, as well as degrade caprolactam. Lactams represent important nylon precursors, and are produced in quantities exceeding one million tons per year (Zhang et al., 2017). To better understand this metabolism we use a combination of Random Barcode Transposon Sequencing (RB-TnSeq) and shotgun proteomics to identify the oplBA locus as the likely responsible amide hydrolase that initiates valerolactam catabolism. Deletion of the oplBA genes prevented P. putida from growing on valerolactam, prevented the degradation of valerolactam in rich media, and dramatically reduced caprolactam degradation under the same conditions. Deletion of oplBA, as well as pathways that compete for precursors L-lysine or 5-aminovalerate, increased the titer of valerolactam from undetectable after 48 h of production to ~90 mg/L. This work may serve as a template to rapidly eliminate undesirable metabolism in non-model hosts in future metabolic engineering efforts.

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Section: Discussionmentioning

confidence: 99%

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer

Thompson

Valencia

Blake-Hedges

et al. 2019

Metabolic Engineering Communications

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“…A great deal of work has been conducted to elucidate the complex catabolism of lysine in P. putida [7,12] , yet relatively little work has been done to increase flux to lysine within the bacterium. While there has been little to divert flux to L-lysine in P. putida , there is a wealth of evidence in other bacteria where high titers of intracellular lysine have been achieved [23,24]. The ever increasing body of research to characterize the sprawling metabolism of P. putida will greatly aid in future efforts of efficient production of valerolactam from lignocellulosic feedstocks.…”

Section: Discussionmentioning

confidence: 99%

Host engineering for improved valerolactam production inPseudomonas putida

Thompson

et al. 2019

Preprint

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25Pseudomonas putida is a promising bacterial chassis for metabolic engineering given its 26 ability to metabolize a wide array of carbon sources, especially aromatic compounds derived 27 from lignin. However, this omnivorous metabolism can also be a hindrance when it can naturally 28 metabolize products produced from engineered pathways. Herein we show that P. putida is able 29 to use valerolactam as a sole carbon source, as well as degrade caprolactam. Lactams represent 30 important nylon precursors, and are produced in quantities exceeding one million tons per 31 year[1]. To better understand this metabolism we use a combination of Random Barcode 32 Transposon Sequencing (RB-TnSeq) and shotgun proteomics to identify the oplBA locus as the 33 likely responsible amide hydrolase that initiates valerolactam catabolism. Deletion of the oplBA 34 genes prevented P. putida from growing on valerolactam, prevented the degradation of 35 valerolactam in rich media, and dramatically reduced caprolactam degradation under the same 36 conditions. Deletion of oplBA, as well as pathways that compete for precursors L-lysine or 5-37 aminovalerate, increased the titer of valerolactam from undetectable after 48 hours of production 38 to ~90 mg/L. This work may serve as a template to rapidly eliminate undesirable metabolism in 39 non-model hosts in future metabolic engineering efforts. 40 1 INTRODUCTION 41 Pseudomonas putida has attracted great attention as a potential chassis organism for 42 metabolic engineering due in large part to its ability to metabolize a wide variety of carbon 43 sources, particularly aromatic compounds that can be derived from lignin [2,3]. To more fully 44 realize this vision, much effort has been put forth recently to better characterize the central 45 metabolism of P. putida with updated genome-scale models [4], C 13 flux experiments [5,6], and 46high-throughput fitness assays, which have all contributed to a more complete understanding of 47 48 fully understood. 49 One consequence of this omnivorous metabolism is that P. putida possesses the ability to 50 degrade or fully catabolize chemicals metabolic engineers seek to produce in the host. An 51 ongoing challenge for P. putida host engineering will be to rapidly identify catabolic pathways 52 of important target molecules and eliminate them from the genome. The recent report of a novel 53 pathway for levulinic acid catabolism in P. putida KT2440 underscores the catabolic flexibility 54 of the host, and an additional obstacle towards producing high product titer [8]. While 55 challenging, this is not surprising; as a genus, Pseudomonads are well known for their ability to 56 degrade a wide range of naturally occurring or xenobiotic chemicals [9,10]. 57 Caprolactam and valerolactam are both important commodity chemicals used in the 58 synthesis of nylon polymers, with global production of caprolactam reaching over four million 59 metric tons [1]. Multiple efforts have been made to produce these chemicals biologically, with 60the titers of valerolactam...

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Comprehensive assessment of the l-lysine production process from fermentation of sugarcane molasses

Anaya-Reza

López‐Arenas

2017

Bioprocess Biosyst Eng

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L-Lysine is an essential amino acid that can be produced by chemical processes from fossil raw materials, as well as by microbial fermentation, the latter being a more efficient and environmentally friendly procedure. In this work, the production process of L-lysine-HCl is studied using a systematic approach based on modeling and simulation, which supports decision making in the early stage of process design. The study considers two analysis stages: first, the dynamic analysis of the fermentation reactor, where the conversion of sugars from sugarcane molasses to L-lysine with a strain of Corynebacterium glutamicum is carried out. In this stage, the operation mode (either batch or fed batch) and operating conditions of the fermentation reactor are defined to reach the maximum technical criteria. Afterwards, the second analysis stage relates to the industrial production process of L-lysine-HCl, where the fermentation reactor, upstream processing, and downstream processing are included. In this stage, the influence of key parameters on the overall process performance is scrutinized through the evaluation of several technical, economic, and environmental criteria, to determine a profitable and sustainable design of the L-lysine production process. The main results show how the operating conditions, process design, and selection of evaluation criteria can influence in the conceptual design. The best plant design shows maximum product yield (0.31 g L-lysine/g glucose) and productivity (1.99 g/L/h), achieving 26.5% return on investment (ROI) with a payback period (PBP) of 3.8 years, decreasing water and energy consumption, and with a low potential environmental impact (PEI) index.

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Lysine overproducing Corynebacterium glutamicum is characterized by a robust linear combination of two optimal phenotypic states

Cited by 4 publications

References 51 publications

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer

Host engineering for improved valerolactam production inPseudomonas putida

Comprehensive assessment of the l-lysine production process from fermentation of sugarcane molasses

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