Building Microbial Factories for the Production of Aromatic Amino Acid
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(12) United States Patent (10) Patent No.: US 8,323,956 B2 Reardon Et Al
USOO8323956B2 (12) United States Patent (10) Patent No.: US 8,323,956 B2 Reardon et al. (45) Date of Patent: Dec. 4, 2012 (54) DISTAL TIP OF BIOSENSORTRANSDUCER 6,159,681 A 12/2000 Zebala COMPRISINGENZYME FOR DEAMINATION 6,265,201 B1 7/2001 Wackett et al. 6,271,015 B1* 8/2001 Gilula et al. .................. 435,228 6,284.522 B1 9, 2001 Wackett et al. (75) Inventors: Kenneth F. Reardon, Fort Collins, CO 6,291,200 B1 9, 2001 LeJeune et al. (US); Lawrence Philip Wackett, St. 6,369,299 B1 4/2002 Sadowsky et al. 6.825,001 B2 11/2004 Wackett et al. Paul, MN (US) 7,381,538 B2 * 6/2008 Reardon et al. ................. 435/23 7.595,181 B2 * 9/2009 Gruning et al. ............... 435/197 (73) Assignee: Colorado State University Research 7,709,221 B2 5, 2010 Rose et al. Foundation, Fort Collins, CO (US) 2004/0265811 A1 12/2004 Reardon et al. 2006/0275855 A1 12/2006 Blackburn et al. .............. 435/15 (*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 U.S.C. 154(b) by 340 days. WO WOO3,O25892 12/1993 OTHER PUBLICATIONS (21) Appl. No.: 12/358,140 PCT/US2009/040121, International Search Report & Written Opin (22) Filed: Jan. 22, 2009 ion mailed Jul. 14, 2009, 8 pages. Adachi, K., et al; Purification and properties of homogentisate (65) Prior Publication Data oxygenase from Pseudomonas fluorescens. Biochim. Biophys. Acta 118 (1966) 88-97. US 2009/0221014 A1 Sep. 3, 2009 Aldridge, W.N.; Serum esterases. -
Metabolic Engineering of Microbial Cell Factories for Biosynthesis of Flavonoids: a Review
molecules Review Metabolic Engineering of Microbial Cell Factories for Biosynthesis of Flavonoids: A Review Hanghang Lou 1,†, Lifei Hu 2,†, Hongyun Lu 1, Tianyu Wei 1 and Qihe Chen 1,* 1 Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China; [email protected] (H.L.); [email protected] (H.L.); [email protected] (T.W.) 2 Hubei Key Lab of Quality and Safety of Traditional Chinese Medicine & Health Food, Huangshi 435100, China; [email protected] * Correspondence: [email protected]; Tel.: +86-0571-8698-4316 † These authors are equally to this manuscript. Abstract: Flavonoids belong to a class of plant secondary metabolites that have a polyphenol structure. Flavonoids show extensive biological activity, such as antioxidative, anti-inflammatory, anti-mutagenic, anti-cancer, and antibacterial properties, so they are widely used in the food, phar- maceutical, and nutraceutical industries. However, traditional sources of flavonoids are no longer sufficient to meet current demands. In recent years, with the clarification of the biosynthetic pathway of flavonoids and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce flavonoids. This article mainly reviews the biosynthetic pathways of flavonoids and the development of microbial expression systems for the production of flavonoids in order to provide a useful reference for further research on synthetic metabolic engineering of flavonoids. Meanwhile, the application of co-culture systems in the biosynthesis of flavonoids is emphasized in this review. Citation: Lou, H.; Hu, L.; Lu, H.; Wei, Keywords: flavonoids; metabolic engineering; co-culture system; biosynthesis; microbial cell factories T.; Chen, Q. -
Developmental Plasticity and Circuit Mechanisms of Dopamine-Modulated Aggression Darshini Mahadevia Submitted in Partial Fulfill
Developmental plasticity and circuit mechanisms of dopamine-modulated aggression Darshini Mahadevia Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2018 © 2018 Darshini Mahadevia All rights reserved ABSTRACT Developmental plasticity and circuit mechanisms of dopamine-modulated aggression Darshini Mahadevia Aggression and violence pose a significant public health concern to society. Aggression is a highly conserved behavior that shares common biological correlates across species. While aggression developed as an evolutionary adaptation to competition, its untimely and uncontrolled expression is maladaptive and presents itself in a number of neuropsychiatric disorders. A mechanistic hypothesis for pathological aggression links aberrant behavior with heightened dopamine function. However, while dopamine hyper-activity is a neural correlate of aggression, the developmental aspects and circuit level contributions of dopaminergic signaling have not been elucidated. In this dissertation, I aim to address these questions regarding the specifics of dopamine function in a murine model of aggressive behavior. In chapter I, I provide a review of the literature that describes the current state of research on aggression. I describe the background elements that lay the foundation for experimental questions and original data presented in later chapters. I introduce, in detail, published studies that describe the clinical manifestation and epidemiological spread, the dominant categories, the anatomy and physiology, and the pharmacology of aggression, with a particular emphasis on the dopaminergic system. Finally, I describe instances of genetic and environmental risk factors impacting aggression, concluding with studies revealing an important role for interactions among genetics, environmental factors, and age in the development of aggression. -
Part One Amino Acids As Building Blocks
Part One Amino Acids as Building Blocks Amino Acids, Peptides and Proteins in Organic Chemistry. Vol.3 – Building Blocks, Catalysis and Coupling Chemistry. Edited by Andrew B. Hughes Copyright Ó 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32102-5 j3 1 Amino Acid Biosynthesis Emily J. Parker and Andrew J. Pratt 1.1 Introduction The ribosomal synthesis of proteins utilizes a family of 20 a-amino acids that are universally coded by the translation machinery; in addition, two further a-amino acids, selenocysteine and pyrrolysine, are now believed to be incorporated into proteins via ribosomal synthesis in some organisms. More than 300 other amino acid residues have been identified in proteins, but most are of restricted distribution and produced via post-translational modification of the ubiquitous protein amino acids [1]. The ribosomally encoded a-amino acids described here ultimately derive from a-keto acids by a process corresponding to reductive amination. The most important biosynthetic distinction relates to whether appropriate carbon skeletons are pre-existing in basic metabolism or whether they have to be synthesized de novo and this division underpins the structure of this chapter. There are a small number of a-keto acids ubiquitously found in core metabolism, notably pyruvate (and a related 3-phosphoglycerate derivative from glycolysis), together with two components of the tricarboxylic acid cycle (TCA), oxaloacetate and a-ketoglutarate (a-KG). These building blocks ultimately provide the carbon skeletons for unbranched a-amino acids of three, four, and five carbons, respectively. a-Amino acids with shorter (glycine) or longer (lysine and pyrrolysine) straight chains are made by alternative pathways depending on the available raw materials. -
L.) Leaves Tao Jiang1,3, Kunyuan Guo2,3, Lingdi Liu1, Wei Tian1, Xiaoliang Xie1, Saiqun Wen1 & Chunxiu Wen1*
www.nature.com/scientificreports OPEN Integrated transcriptomic and metabolomic data reveal the favonoid biosynthesis metabolic pathway in Perilla frutescens (L.) leaves Tao Jiang1,3, Kunyuan Guo2,3, Lingdi Liu1, Wei Tian1, Xiaoliang Xie1, Saiqun Wen1 & Chunxiu Wen1* Perilla frutescens (L.) is an important medicinal and edible plant in China with nutritional and medical uses. The extract from leaves of Perilla frutescens contains favonoids and volatile oils, which are mainly used in traditional Chinese medicine. In this study, we analyzed the transcriptomic and metabolomic data of the leaves of two Perilla frutescens varieties: JIZI 1 and JIZI 2. A total of 9277 diferentially expressed genes and 223 favonoid metabolites were identifed in these varieties. Chrysoeriol, apigenin, malvidin, cyanidin, kaempferol, and their derivatives were abundant in the leaves of Perilla frutescens, which were more than 70% of total favonoid contents. A total of 77 unigenes encoding 15 enzymes were identifed as candidate genes involved in favonoid biosynthesis in the leaves of Perilla frutescens. High expression of the CHS gene enhances the accumulation of favonoids in the leaves of Perilla frutescens. Our results provide valuable information on the favonoid metabolites and candidate genes involved in the favonoid biosynthesis pathways in the leaves of Perilla frutescens. Perilla frutescens (L.), which is a self-compatible annual herb, belongs to the family Lamiaceae. Tis species has been widely cultivated in China, Japan, and Korea for centuries. Perilla frutescens is an important medicinal and edible plant in China with medical and nutritional uses 1. Its leaves can be utilized as a transitional medicinal herb, as a vegetable, and as a spice, and its seeds can be processed into foods and nutritional edible oils 2. -
JAD 5478.Pdf
JAD-05478; No of Pages 9 Journal of Affective Disorders xxx (2012) xxx–xxx Contents lists available at SciVerse ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad Research report Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms Armen K. Goenjian a,b,e,⁎, Julia N. Bailey c,d, David P. Walling b, Alan M. Steinberg a, Devon Schmidt b, Uma Dandekar d, Ernest P. Noble e a UCLA/Duke University National Center for Child Traumatic Stress, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles (UCLA), United States b Collaborative Neuroscience Network, Garden Grove, CA 92845, United States c Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, United States d Epilepsy Genetics/Genomics Laboratories, VA GLAHS, Los Angeles, CA, United States e Alcohol Research Center, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, United States article info abstract Article history: Objective: To examine the potential contribution of the serotonin hydroxylase (TPH1 and Received 29 January 2012 TPH2) genes, and the serotonin transporter promoter polymorphism (5HTTLPR) to the unique Accepted 5 February 2012 and pleiotropic risk of PTSD symptoms and depressive symptoms. Available online xxxx Methods: Participants included 200 adults exposed to the 1988 Spitak earthquake from 12 multigenerational families (3 to 5 generations). Severity of trauma exposure, PTSD, and de- Keywords: pressive symptoms were assessed using standard psychometric instruments. Pedigree-based Genetics variance component analysis was used to assess the association between select genes and PTSD the phenotypes. Depression Results: After adjusting for age, sex, exposure and environmental variables, there was a signif- Tryptophan hydroxylase icant association of PTSD symptoms with the ‘t’ allele of TPH1 SNP rs2108977 (pb0.004), Serotonin transporter explaining 3% of the phenotypic variance. -
Thermophilic Bacteria Are Potential Sources of Novel Rieske Non-Heme
Chakraborty et al. AMB Expr (2017) 7:17 DOI 10.1186/s13568-016-0318-5 ORIGINAL ARTICLE Open Access Thermophilic bacteria are potential sources of novel Rieske non‑heme iron oxygenases Joydeep Chakraborty, Chiho Suzuki‑Minakuchi, Kazunori Okada and Hideaki Nojiri* Abstract Rieske non-heme iron oxygenases, which have a Rieske-type [2Fe–2S] cluster and a non-heme catalytic iron center, are an important family of oxidoreductases involved mainly in regio- and stereoselective transformation of a wide array of aromatic hydrocarbons. Though present in all domains of life, the most widely studied Rieske non-heme iron oxygenases are found in mesophilic bacteria. The present study explores the potential for isolating novel Rieske non- heme iron oxygenases from thermophilic sources. Browsing the entire bacterial genome database led to the identifi‑ cation of 45 homologs from thermophilic bacteria distributed mainly among Chloroflexi, Deinococcus–Thermus and Firmicutes. Thermostability, measured according to the aliphatic index, showed higher values for certain homologs compared with their mesophilic relatives. Prediction of substrate preferences indicated that a wide array of aromatic hydrocarbons could be transformed by most of the identified oxygenase homologs. Further identification of putative genes encoding components of a functional oxygenase system opens up the possibility of reconstituting functional thermophilic Rieske non-heme iron oxygenase systems with novel properties. Keywords: Rieske non-heme iron oxygenase, Oxidoreductase, Thermophiles, Aromatic hydrocarbons, Biotransformation Introduction of a wide array of agrochemically and pharmaceutically Rieske non-heme iron oxygenases (ROs) constitute a important compounds (Ensley et al. 1983; Wackett et al. large family of oxidoreductase enzymes involved primar- 1988; Hudlicky et al. -
Yeast Genome Gazetteer P35-65
gazetteer Metabolism 35 tRNA modification mitochondrial transport amino-acid metabolism other tRNA-transcription activities vesicular transport (Golgi network, etc.) nitrogen and sulphur metabolism mRNA synthesis peroxisomal transport nucleotide metabolism mRNA processing (splicing) vacuolar transport phosphate metabolism mRNA processing (5’-end, 3’-end processing extracellular transport carbohydrate metabolism and mRNA degradation) cellular import lipid, fatty-acid and sterol metabolism other mRNA-transcription activities other intracellular-transport activities biosynthesis of vitamins, cofactors and RNA transport prosthetic groups other transcription activities Cellular organization and biogenesis 54 ionic homeostasis organization and biogenesis of cell wall and Protein synthesis 48 plasma membrane Energy 40 ribosomal proteins organization and biogenesis of glycolysis translation (initiation,elongation and cytoskeleton gluconeogenesis termination) organization and biogenesis of endoplasmic pentose-phosphate pathway translational control reticulum and Golgi tricarboxylic-acid pathway tRNA synthetases organization and biogenesis of chromosome respiration other protein-synthesis activities structure fermentation mitochondrial organization and biogenesis metabolism of energy reserves (glycogen Protein destination 49 peroxisomal organization and biogenesis and trehalose) protein folding and stabilization endosomal organization and biogenesis other energy-generation activities protein targeting, sorting and translocation vacuolar and lysosomal -
A Systematic Review on Main Chemical Constituents of Papaver Bracteatum
Journal of Medicinal Plants A Systematic Review on Main Chemical Constituents of Papaver bracteatum Soleymankhani M (Ph.D. student), Khalighi-Sigaroodi F (Ph.D.)*, Hajiaghaee R (Ph.D.), Naghdi Badi H (Ph.D.), Mehrafarin A (Ph.D.), Ghorbani Nohooji M (Ph.D.) Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran * Corresponding author: Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, P.O.Box: 33651/66571, Karaj, Iran Tel: +98 - 26 - 34764010-9, Fax: +98 - 26-34764021 E-mail: [email protected] Received: 17 April 2013 Accepted: 12 Oct. 2014 Abstract Papaver bracteatum Lindly (Papaveraceae) is an endemic species of Iran which has economic importance in drug industries. The main alkaloid of the plant is thebaine which is used as a precursor of the semi-synthetic and synthetic compounds including codeine and naloxone, respectively. This systematic review focuses on main component of Papaver bracteatum and methods used to determine thebaine. All studies which assessed the potential effect of the whole plant or its extract on clinical or preclinical studies were reviewed. In addition, methods for determination of the main components, especially thebaine, which have been published from 1948 to March 2013, were included. Exclusion criteria were agricultural studies that did not assess. This study has listed alkaloids identified in P. bracteatum which reported since 1948 to 2013. Also, the biological activities of main compounds of Papaver bracteatum including thebaine, isothebaine, (-)-nuciferine have been reviewed. As thebaine has many medicinal and industrial values, determination methods of thebaine in P. bracteatum were summarized. The methods have being used for determination of thebaine include chromatographic (HPLC, GC and TLC) and non chromatographic methods. -
Genomic Analyses of Unique Carbohydrate and Phytohormone Metabolism in the Macroalga Gracilariopsis Lemaneiformis (Rhodophyta)
Sun et al. BMC Plant Biology (2018) 18:94 https://doi.org/10.1186/s12870-018-1309-2 RESEARCH ARTICLE Open Access Genomic analyses of unique carbohydrate and phytohormone metabolism in the macroalga Gracilariopsis lemaneiformis (Rhodophyta) Xue Sun1, Jun Wu2, Guangce Wang3, Yani Kang1,2, Hong Sain Ooi4, Tingting Shen2, Fangjun Wang1, Rui Yang1, Nianjun Xu1* and Xiaodong Zhao2* Abstract Background: Red algae are economically valuable for food and in industry. However, their genomic information is limited, and the genomic data of only a few species of red algae have been sequenced and deposited recently. In this study, we annotated a draft genome of the macroalga Gracilariopsis lemaneiformis (Gracilariales, Rhodophyta). Results: The entire 88.98 Mb genome of Gp. lemaneiformis 981 was generated from 13,825 scaffolds (≥500 bp) with an N50 length of 30,590 bp, accounting for approximately 91% of this algal genome. A total of 38.73 Mb of scaffold sequences were repetitive, and 9281 protein-coding genes were predicted. A phylogenomic analysis of 20 genomes revealed the relationship among the Chromalveolata, Rhodophyta, Chlorophyta and higher plants. Homology analysis indicated phylogenetic proximity between Gp. lemaneiformis and Chondrus crispus. The number of enzymes related to the metabolism of carbohydrates, including agar, glycoside hydrolases, glycosyltransferases, was abundant. In addition, signaling pathways associated with phytohormones such as auxin, salicylic acid and jasmonates are reported for the first time for this alga. Conclusion: We sequenced and analyzed a draft genome of the red alga Gp. lemaneiformis, and revealed its carbohydrate metabolism and phytohormone signaling characteristics. This work will be helpful in research on the functional and comparative genomics of the order Gracilariales and will enrich the genomic information on marine algae. -
Genome-Scale Fitness Profile of Caulobacter Crescentus Grown in Natural Freshwater
Supplemental Material Genome-scale fitness profile of Caulobacter crescentus grown in natural freshwater Kristy L. Hentchel, Leila M. Reyes Ruiz, Aretha Fiebig, Patrick D. Curtis, Maureen L. Coleman, Sean Crosson Tn5 and Tn-Himar: comparing gene essentiality and the effects of gene disruption on fitness across studies A previous analysis of a highly saturated Caulobacter Tn5 transposon library revealed a set of genes that are required for growth in complex PYE medium [1]; approximately 14% of genes in the genome were deemed essential. The total genome insertion coverage was lower in the Himar library described here than in the Tn5 dataset of Christen et al (2011), as Tn-Himar inserts specifically into TA dinucleotide sites (with 67% GC content, TA sites are relatively limited in the Caulobacter genome). Genes for which we failed to detect Tn-Himar insertions (Table S13) were largely consistent with essential genes reported by Christen et al [1], with exceptions likely due to differential coverage of Tn5 versus Tn-Himar mutagenesis and differences in metrics used to define essentiality. A comparison of the essential genes defined by Christen et al and by our Tn5-seq and Tn-Himar fitness studies is presented in Table S4. We have uncovered evidence for gene disruptions that both enhanced or reduced strain fitness in lake water and M2X relative to PYE. Such results are consistent for a number of genes across both the Tn5 and Tn-Himar datasets. Disruption of genes encoding three metabolic enzymes, a class C β-lactamase family protein (CCNA_00255), transaldolase (CCNA_03729), and methylcrotonyl-CoA carboxylase (CCNA_02250), enhanced Caulobacter fitness in Lake Michigan water relative to PYE using both Tn5 and Tn-Himar approaches (Table S7). -
( 12 ) United States Patent
US010167477B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 167, 477 B2 Pharkya (45 ) Date of Patent : Jan . 1 , 2019 ( 54 ) MICROORGANISMS AND METHODS FOR 5 , 143, 834 A 9 / 1992 Glassner et al . 5 , 168 ,055 A 12 / 1992 Datta et al. THE PRODUCTION OF ANILINE 5 , 168 ,056 A 12 / 1992 Frost .. .. 435 / 472 5 , 173 ,429 A 12/ 1992 Gaddy et al. (71 ) Applicant: Genomatica , Inc. , San Diego , CA (US ) 5 , 182 , 199 A 1 / 1993 Hartley 5 , 192 ,673 A 3 / 1993 Jain et al . (72 ) Inventor : Priti Pharkya, San Diego , CA (US ) 5 , 403 , 721 A 4 / 1995 Ward , Jr . et al. 5 ,413 , 922 A 5 / 1995 Matsuyama et al. 5 ,416 , 020 A 5 / 1995 Severson et al . (73 ) Assignee : GENOMATICA , INC . , San Diego, CA 5 ,457 , 040 A 10 / 1995 Jarry et al . (US ) 5 ,478 , 952 A 12 / 1995 Schwartz 5 ,487 ,987 A 1 / 1996 Frost et al. ( * ) Notice : Subject to any disclaimer, the term of this 5 , 504 ,004 A 4 / 1996 Guettler et al. patent is extended or adjusted under 35 5 , 521 ,075 A 5 / 1996 Guettler et al . U . S . C . 154 ( b ) by 0 days. 5 ,573 , 931 A 11/ 1996 Guettler et al. 5 ,616 , 496 A 4 / 1997 Frost et al. 5 ,686 ,276 A 11 / 1997 Lafend et al . ( 21 ) Appl. No. : 15 /914 , 308 5 ,700 , 934 A 12 / 1997 Wolters et al. 5 ,770 ,435 A 6 / 1998 Donnelly et al . (22 ) Filed : Mar. 7 , 2018 5 , 807 , 722 A 9 / 1998 Gaddy et al .