Improvement of retinoids production in recombinant E. coli using glyoxylic acid

Isoprenoids are the most chemically diverse compounds found in nature. They are present in all organisms and have essential roles in membrane structure, redox chemistry, reproductive cycles, growth regulation, signal transduction and defense mechanisms. In spite of their diversity of functions and structures, all isoprenoids are derived from the common building blocks of isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). Optimization of IPP synthesis pathway is of benefit to mass production of various isoprenoids. There are two pathways of 2-C-Methyl-D-erythritol-4-phosphate (MEP) and mevalonate (MVA) for IPP synthesis. Prokaryotes including E. coli generally use MEP pathway whereas MVA pathway is used in eukaryotes. To improve isoprenoid production, it was performed the deletion of genes in E. coli, which are involved in both formation of fermentation by-products such as organic acids and alcohols, and consumption of precursors of MEP and MVA pathways, pyruvate and acetyl-CoA. As a result, we were able to develop a strain with improved fermentation productivity and carbon source utilization efficiency, the mutant strain was called AceCo. Higher lycopene production was achieved in the AceCo strain compared to the wild type MG1655 strain due to no formation of the inhibitory by-products. However, retinoids production of AceCo strain decreased to a half of that of MG1655 strain. Please click Additional Files below to see the full abstract

Sequential whole cell conversion process for production of D-psicose and D- mannitol from D-fructose

Rare sugars, which exist only limited quantities naturally, have received considerable attention because of its various specific nutritional and biological functions. Likewise, D-psicose (D-ribo-2-hexulose or D-allulose), a C-3 epimer of D-fructose, has many uses which include reducing intra-abdominal fat accumulation, protecting pancreas beta-islets and improving insulin sensitivity. Especially, D-psicose has only 0.3% calories compared to sucrose, while it has 70% relative sweetness. Additionally, in 2012, D-psicose was approved as a food additive and designated as Generally Recognized As Safe (GRAS) by Food and Drug Administration (FDA). Despite such abundant advantages, there is no economical way of mass production of D-psicose. Recently, biological production of D-psicose from D-fructose using D-psicose 3-epimerase (DPE) has been developed. However, the conversion yield is below 30%, which causes an undesirable increase of purification cost because of the similar solubility of D-psicose and D-fructose. Thus, we addressed the problem by converting the residual fructose, after the reaction of D-psicose production, to D-mannitol, which has a low solubility. The sequential whole cell conversion reactions for D-psicose and D-mannitol allow a convenient and economic purification of both products. This work was supported by a grant from the Next-Generation BioGreen 21 Program (SSAC, grant#: PJ01106201), RDA, Korea. Reference 1) Carsten Bäumchen & Stephanie Bringer-Meyer (2007), Expression of glf Z.m. increases D-mannitol formation in whole cell biotransformation with resting cells of Corynebacterium glutamicum, Appl Microbiol Biotechnol 76(3):545–52. 2) Ortiz, M. E., Bleckwedel, J., Raya, R. R., & Mozzi, F. (2013). Biotechnological and in situ food production of polyols by lactic acid bacteria, Appl Microbiol Biotechnol 97:4713-4726 3) Park, Y., Oh, E. J., Jo, J., Jin, Y., & Seo, J. (2016). Recent advances in biological production of sugar alcohols. Curr Opin Biotechnol 37:105–113

PD-1 deficiency protects experimental colitis via alteration of gut microbiota

Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 (PD-1(-/-)) did not develop colon inflammation. Interestingly, PD-1(-/-) mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of PD-1(-/-) mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that PD-1(-/-) mice had altered composition of gut microbiota with significant reduction in Rikenellaceae family. These altered colon bacteria of PD-1(-/-) mice induced less amount of inflammatory mediators from colon epithelial cells, including interleukin (IL)-6, and inflammatory chemokines. Taken together, our study indicates that PD-1 expression is involved in the resistance to experimental colitis through altered bacterial communities of colon.112Ysciescopuskc