Lysine Fermentation: History and Genome Breeding

Lysine fermentation by Corynebacterium glutamicum was developed in 1958 by Kyowa Hakko Kogyo Co. Ltd. (current Kyowa Hakko Bio Co. Ltd.) and is the second oldest amino acid fermentation process after glutamate fermentation. The fundamental mechanism of lysine production, discovered in the early stages of the process's history, gave birth to the concept known as "metabolic regulatory fermentation,"which is now widely applied to metabolite production. After the development of rational metabolic engineering, research on lysine production first highlighted the need for engineering of the central metabolism from the viewpoints of precursor supply and NADPH regeneration. Furthermore, the existence of active export systems for amino acids was first demonstrated for lysine in C. glutamicum, and this discovery has resulted in the current recognition of such exporters as an important consideration in metabolite production. Lysine fermentation is also notable as the first process to which genomics was successfully applied to improve amino acid production. The first global "genome breeding" strategy was developed using a lysine producer as a model; this has since led to new lysine producers that are more efficient than classical industrial producers. These advances in strain development technology, combined with recent systems-level approaches, have almost achieved the optimization of entire cellular systems as cell factories for lysine production. In parallel, the continuous improvement of the process has resulted not only in fermentation processes with reduced load on downstream processing but also in commercialization of various product forms according to their intended uses. Nowadays lysine fermentation underpins a giant lysine demand of more than 2 million metric tons per year.ArticleIn: Yokota A., Ikeda M. (eds) Amino Acid Fermentation. Advances in Biochemical Engineering/Biotechnology, 159:73-102 (2017)journal articl

Sugar transport systems in Corynebacterium glutamicum: features and applications to strain development

Corynebacterium glutamicum uses the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) to take up and phosphorylate glucose, fructose, and sucrose, the major sugars from agricultural crops that are used as the primary feedstocks for industrial amino acid fermentation. This means that worldwide amino acid production using this organism has depended exclusively on the PTS. Recently, a better understanding not only of PTS-mediated sugar uptake but also of global regulation associated with the PTS has permitted the correction of certain negative aspects of this sugar transport system for amino acid production. In addition, the recent identification of different glucose uptake systems in this organism has led to a strategy for the generation of C. glutamicum strains that express non-PTS routes instead of the original PTS. The potential practical advantages of the development of such strains are discussed.ArticleAPPLIED MICROBIOLOGY AND BIOTECHNOLOGY. 96(5):1191-1200 (2012)journal articl

Lysine-Independent Ubiquitination of Epstein–Barr Virus LMP2A

AbstractLatent membrane protein 2A (LMP2A) of latent Epstein–Barr virus (EBV) specifically associates with HECT domain-containing Nedd4-family ubiquitin-protein ligases (E3s). Here we demonstrate that LMP2A is specifically ubiquitinated by the HECT domains of AIP4 and WWP2. Deletion and site-specific mutation of LMP2A indicates that LMP2A is ubiquitinated at its amino-terminus and is not ubiquitinated on lysine residues. LMP2A and LMP1, also encoded by EBV, are two of only four proteins that have been identified that are ubiquitinated at the amino-terminus, indicating that EBV may specifically target and utilize this host cell protein modification

Neural style transfer of weak lensing mass maps

We propose a new generative model of projected cosmic mass density maps inferred from weak gravitational lensing observations of distant galaxies (weak lensing mass maps). We construct the model based on a neural style transfer so that it can transform Gaussian weak lensing mass maps into deeply non-Gaussian counterparts as predicted in ray-tracing lensing simulations. We develop an unpaired image-to-image translation method with Cycle-Consistent Generative Adversarial Networks (Cycle GAN), which learn efficient mapping from an input domain to a target domain. Our model is designed to enjoy important advantages; it is trainable with no need for paired simulation data, flexible to make the input domain visually meaningful, and expandable to rapidly-produce a map with a larger sky coverage than training data without additional learning. Using 10,000 lensing simulations, we find that appropriate labeling of training data based on field variance requires the model to exhibit a desired diversity of various summary statistics for weak lensing mass maps. Compared with a popular log-normal model, our model improves in predicting the statistical natures of three-point correlations and local properties of rare high-density regions. We also demonstrate that our model enables us to produce a continuous map with a sky coverage of $\sim166\, \mathrm{deg}^2$ but similar non-Gaussian features to training data covering $\sim12\, \mathrm{deg}^2$ in a GPU minute. Hence, our model can be beneficial to massive productions of synthetic weak lensing mass maps, which is of great importance in future precise real-world analyses.Comment: 20 pages, 11 figures, 3 tables. A trial dataset of fake weak lensing mass maps generated by our GANs is available at https://www.dropbox.com/scl/fo/hq1o41e8jwsfm4gqtkmnu/h?rlkey=0ymsucz2nzoju3gew8tsyz7qw&dl=

Corynebacterium glutamicum芳香族アミノ酸生産菌の分子育種に関する研究

本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである京都大学0048新制・論文博士博士(農学)乙第8803号論農博第1966号新制||農||695(附属図書館)学位論文||H7||N2779(農学部図書室)UT51-95-B268(主査)教授 駒野 徹, 教授 大山 莞爾, 教授 加藤 暢夫学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDFA