DOCSLIB.ORG

Engineered Cells for Production of Indole-Derivatives

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Engineered Cells for Production of Indole-Derivatives Downloaded from orbit.dtu.dk on: Oct 05, 2021 Engineered cells for production of indole-derivatives Kell, Douglas; Yang, Lei; Malla, Sailesh Publication date: 2020 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Kell, D., Yang, L., & Malla, S. (2020). Engineered cells for production of indole-derivatives. (Patent No. WO2020187739). General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. ) ( 2 (51) International Patent Classification: C07K 14/715 (2006.01) (21) International Application Number: PCT/EP2020/056828 (22) International Filing Date: 13 March 2020 (13.03.2020) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 19163 184.5 15 March 2019 (15.03.2019) EP (71) Applicant: DANMARKS TEKNISKE UNIVERSITET [DK/DK]; Anker Engelunds Vej 101 A, 2800 Kgs. Lyngby (DK). (72) Inventors: KELL, Douglas, Bruce; Chirk Manor, Trevor Rd, Chirk, Wrexham LL14 5HD (GB). YANG, Lei; Hojbovej 7A, 3460 Birkerod (DK). MALLA, Sailesh; Slaenhoj 18, 2990 Niva (DK). (74) Agent: INSPICOS P/S; Kogle Alle 2, 2970 Horsholm (DK). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — of inventorship (Rule 4.17 (iv)) Published: — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a)) (54) Title: ENGINEERED CELLS FOR PRODUCTION OF INDOLE-DERIVATIVES (57) Abstract: Integral membrane proteins capable of transporting melatonin and other indole-derivatives across biological membranes, and uses thereof. ENGINEERED CELLS FOR PRODUCTION OF INDOLE-DERIVATIVES FIELD OF THE INVENTION The present invention relates to integ ral membra ne proteins ca pable of tra nsporting melatonin and other indole-derivatives across biologica l membra nes, and well as the use of such integra l membra ne proteins in cell factories for production of melaton in and other indole-derivatives. BACKGROUND OF THE INVENTION Melatonin is an antioxida nt hormone prod uced in mamma ls that can be used for treating sleep disorders. One of the intermediates in the biolog ica l pathway for prod uction of melatonin ; 5-hyd roxy-L-tryptophan (5HTP), has also been used as a sleep aid as well as an antidepressa nt. Commercia l prod uction of melatonin and 5HTP has so far predomina ntly relied on chemical synthesis, or, in the case of 5HTP, extraction from plants. Producing ' natural' melatonin or 5HTP biolog ica lly in so-ca lled cell factories, i.e ., cells eng ineered to prod uce these compounds, would be high ly desira ble. Such recombinant production of melatonin, 5HTP and other indole-derivatives from tryptopha n is described in, e .g., WO 2013/ 1279 15 Al, WO 2015/0329 11 Al, WO 2017/ 167866 Al, WO 2017/202897 A 1 and WO 2018/037098 A 1 (Danma rks Tekniske Universitet) . Tra nsporters are responsible for cellular exchange of both sma ll molecules and macromolecules (Kell, 20 18; WO13093737 Al (BASF)) . Transporters ca n be engineered to decrease intracellular prod uct concentration, improve substrate uptake, red uce feedback inh ibition or improve cellular growth . Transporters ca n therefore play an important role in bio-based production for improving product titers in fermentation as well as facilitating downstrea m purification process. EP2267 145 Al (Evonik Degussa GmbH) relates to a process for the prod uction of L-amino acids, in particu lar L-threonine, in recombina nt microorga nisms of the family Enterobacteriaceae, in which at the open read ing fra me (ORF) of yhaO is deleted, optiona lly together with a deletion or downregulation of, e .g., yhjV. UniProtKB data base entry P37660 (YHJV_ECOLI) describes E. coli protein YhjV as an inner membra ne tra nsport protein, based on phylogenetic grounds. Sa rgentin i et al. (20 18) reports a screen for genes involved in rad iation surviva l of E. coli, mentioning yhjV among the genes identified . Despite these and other prog resses in the art, however, there is a need for recombinant cells and their use in methods provid ing for cost-effective prod uction of melatonin, 5HTP and other desira ble bioprod ucts. So, one object of the invention is to identify transporters useful for engineering cells towards improved export of melatonin, 5HTP and other indole-derivatives. SUM MARY OF THE INVENTION I n a first aspect, the present invention relates to a recombinant cell comprising a biosynthetic pathway for producing an indole-derivative selected from melatonin, N-acetylseroton in, serotonin and 5-hyd roxytryptopha n (5HTP), wherein the recombina nt cell is genetica lly mod ified to overexpress a gene encod ing an integ ral membrane protein selected from YhjV (SEQ I D NO :2), GarP (SEQ I D N0 :4), ArgO (SEQ I D NO :6), AcrAB (SEQ I D NOS : 10 and 12) and LysP (SEQ I D NO :8), a functiona lly active varia nt and/or frag ment of any thereof, or a combination of any two or more thereof, and wherein the amino acid seq uence of the variant has a sequence identity of at least about 80 % to the amino acid seq uence of the integra l membrane protein and the fragment comprises at least about 80 % of the amino acid sequence of the integ ral membrane protein . I n some embod iments, the recombina nt cell overexpresses a gene encod ing YhjV, Ga rP, ArgO or AcrAB, or a combination of any two or more thereof. I n some embodiments, the recombina nt cell overexpresses a gene encod ing YhjV or a functiona lly active varia nt thereof. I n some embodiments, the biosynthetic pathway comprises (a) an L-tryptopha n hyd roxylase; (b) an L-tryptophan hydroxylase and a 5HTP deca rboxylase; (c) an L-tryptopha n hyd roxylase, a 5HTP deca rboxylase, and a serotonin acetyltra nsferase; (d) an L-tryptopha n hyd roxylase, a 5HTP deca rboxylase, a serotonin acetyltra nsferase and an acetylserotonin O- methyltra nsferase; (e) a tryptophan decarboxylase and a tryptamine 5-hyd roxylase; (f) a tryptopha n deca rboxylase; a tryptamine 5-hyd roxylase, and a seroton in acetyltra nsferase; or (g) a tryptophan deca rboxylase; a tryptamine 5-hydroxylase, a seroton in acetyltransferase and an acetylserotonin O-methyltra nsferase. I n some embodiments, the overexpression of the gene encod ing the integ ral membrane protein provides for an increased prod uction of the indole-derivative, an increased tolera nce to the indole-derivative, or both, by the recombina nt cell as compa red to a non-mod ified control cell. I n a second aspect, the invention relates to a recombina nt cell ca pa ble of producing a second indole-derivative from a first indole-derivative via a biosynthetic pathway, wherein the recombinant cell is genetica lly mod ified to overexpress a gene encod ing YhjV (SEQ I D NO :2), or a functiona lly active varia nt and/or frag ment thereof, wherein the amino acid sequence of the variant has a seq uence identity of at least about 80% to SEQ I D NO :2 and the frag ment comprises at least about 80% of SEQ I D NO :2 . I n some embodiments, the recombina nt cell overexpresses a gene encod ing YhjV or a functiona lly active varia nt thereof. I n some embodiments, the first and second indole- derivatives are : (a) tryptopha n and melatonin, respectively; (b) tryptopha n and N- acetylserotonin, respectively; (c) tryptophan and serotonin, respectively; and (d) tryptophan and 5-hyd roxytryptophan, respectively. I n some embodiments, the overexpression of the gene encod ing YhjV or the functiona lly active varia nt and/or frag ment thereof provides for an increased prod uction of the second indole-derivative, an increased tolerance to the second indole-derivative, or both, by the recombinant cell as compa red to a non-modified control cell.
Load more

Recommended publications
  • Consolidated Version of the Sanpin 2.3.2.1078-01 on Food, Raw Material, and Foodstuff
    Registered with the Ministry of Justice of the RF, March 22, 2002 No. 3326 MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION CHIEF STATE SANITARY INSPECTOR OF THE RUSSIAN FEDERATION RESOLUTION No. 36 November 14, 2001 ON ENACTMENT OF SANITARY RULES (as amended by Amendments No.1, approved by Resolution No. 27 of Chief State Sanitary Inspector of the RF dated 20.08.2002, Amendments and Additions No. 2, approved by Resolution No. 41 of Chief State Sanitary Inspector of the RF dated15.04.2003, No. 5, approved by Resolution No. 42 of Chief State Sanitary Inspector of the RF dated 25.06.2007, No. 6, approved by Resolution No. 13 of Chief State Sanitary Inspector of the RF dated 18.02.2008, No. 7, approved by Resolution No. 17 of Chief State Sanitary Inspector of the RF dated 05.03.2008, No. 8, approved by Resolution No. 26 of Chief State Sanitary Inspector of the RF dated 21.04.2008, No. 9, approved by Resolution No. 30 of Chief State Sanitary Inspector of the RF dated 23.05.2008, No. 10, approved by Resolution No. 43 of Chief State Sanitary Inspector of the RF dated 16.07.2008, Amendments No.11, approved by Resolution No. 56 of Chief State Sanitary Inspector of the RF dated 01.10.2008, No. 12, approved by Resolution No. 58 of Chief State Sanitary Inspector of the RF dated 10.10.2008, Amendment No. 13, approved by Resolution No. 69 of Chief State Sanitary Inspector of the RF dated 11.12.2008, Amendments No.14, approved by Resolution No.
    [Show full text]
  • Triptans Step Therapy/Quantity Limit Criteria
    Triptans Step Therapy/Quantity Limit Criteria Program may be implemented with the following options 1) step therapy 2) quantity limits or 3) step therapy with quantity limits For Blue Cross and Blue Shield of Illinois Option 1 (step therapy only) will apply. Brand Generic Dosage Form Amerge® naratriptan tablets Axert® almotriptan tablets Frova® frovatriptan tablets Imitrex® sumatriptan injection*, nasal spray, tablets* Maxalt® rizatriptan tablets Maxalt-MLT® rizatriptan tablets Relpax® eletriptan tablets Treximet™ sumatriptan and naproxen tablets Zomig® zolmitriptan tablets, nasal spray Zomig-ZMT® zolmitriptan tablets * generic available and included as target agent in quantity limit edit FDA APPROVED INDICATIONS1-7 The following information is taken from individual drug prescribing information and is provided here as background information only. Not all FDA-approved indications may be considered medically necessary. All criteria are found in the section “Prior Authorization Criteria for Approval.” Amerge® Tablets1, Axert® Tablets2, Frova® Tablets3,Imitrex® injection4, Imitrex Nasal Spray5, Imitrex Tablets6, Maxalt® Tablets7, Maxalt-MLT® Tablets7, Relpax® Tablets8, Treximet™ Tablets9, Zomig® Tablets10, Zomig-ZMT® Tablets10, and Zomig® Nasal Spray11 Amerge (naratriptan), Axert (almotriptan), Frova (frovatriptan), Imitrex (sumatriptan), Maxalt (rizatriptan), Maxalt-MLT (rizatriptan orally disintegrating), Relpax (eletriptan), Treximet (sumatriptan/naproxen), Zomig (zolmitriptan), and Zomig-ZMT (zolmitriptan orally disintegrating) tablets, and Imitrex (sumatriptan) and Zomig (zolmitriptan) nasal spray are all indicated for the acute treatment of migraine attacks with or without aura in adults. They are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of all of these products have not been established for cluster headache, which is present in an older, predominantly male population.
    [Show full text]
  • Medication Guide 2012
    DeKalb County D.U.I. Court Supervised Treatment Program MEDICATION GUIDE Medication Guide 2012 DeKalb County State Court Decatur, Georgia xxi ********** WELCOME TO THE DEKALB COUNTY D.U.I. COURT SUPERVISED TREATMENT PROGRAM. This 2012 Medication Guide was developed as a collaborative effort by Becky Pirouz, Pharm.D., Director of Pharmacy, Peachford Hospital, and by Lois Michalove, Treatment Coordinator for the DeKalb County D.U.I. Court Supervised Treatment Program, both of whom have extensive experience in addiction recovery and treatment. ********** The following information is intended to assist you in making decisions about medications. This may include those medications that you are prescribed and/or your selection of over-the-counter (OTC) products. Unintended exposure may compromise your treatment program. This is not an exhaustive list, but contains some of the medications that are most commonly used. If in doubt, always consult the Treatment Coordinator. Please inform your physician, dentist, pharmacist and other health care professionals that you are in a recovery program. WE ARE A ZERO-TOLERANCE PROGRAM! DO NOT COMPROMISE YOUR RECOVERY BY MAKING HIGH-RISK CHOICES! xxii - Section 1 – Drugs To Avoid The following drugs must not be used at any time. They are well known to be abused and even small amounts may result in relapse and are contraindicated in your treatment program. However, extenuating circumstances may occur which necessitates the short- term limited use of some of the drugs on this list in consultation with your physician, the Judge and the Treatment Coordinator. This decision should be made prior to your ingestion of any of the Drugs to Avoid.
    [Show full text]
  • WO 2013/116261 A2 8 August 2013 (08.08.2013) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/116261 A2 8 August 2013 (08.08.2013) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every CUD 3/386 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US2013/023728 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, 30 January 2013 (30.01 .2013) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (25) Filing Language: English NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (26) Publication Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (30) Priority Data: ZM, ZW. 12000745.5 3 February 2012 (03.02.2012) EP 12001034.3 16 February 2012 (16.02.2012) EP (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: THE PROCTER & GAMBLE COMPANY GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, [US/US]; One Procter & Gamble Plaza, Cincinnati, Ohio UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 45202 (US).
    [Show full text]
  • Guideline for Preoperative Medication Management
    Guideline: Preoperative Medication Management Guideline for Preoperative Medication Management Purpose of Guideline: To provide guidance to physicians, advanced practice providers (APPs), pharmacists, and nurses regarding medication management in the preoperative setting. Background: Appropriate perioperative medication management is essential to ensure positive surgical outcomes and prevent medication misadventures.1 Results from a prospective analysis of 1,025 patients admitted to a general surgical unit concluded that patients on at least one medication for a chronic disease are 2.7 times more likely to experience surgical complications compared with those not taking any medications. As the aging population requires more medication use and the availability of various nonprescription medications continues to increase, so does the risk of polypharmacy and the need for perioperative medication guidance.2 There are no well-designed trials to support evidence-based recommendations for perioperative medication management; however, general principles and best practice approaches are available. General considerations for perioperative medication management include a thorough medication history, understanding of the medication pharmacokinetics and potential for withdrawal symptoms, understanding the risks associated with the surgical procedure and the risks of medication discontinuation based on the intended indication. Clinical judgement must be exercised, especially if medication pharmacokinetics are not predictable or there are significant risks associated with inappropriate medication withdrawal (eg, tolerance) or continuation (eg, postsurgical infection).2 Clinical Assessment: Prior to instructing the patient on preoperative medication management, completion of a thorough medication history is recommended – including all information on prescription medications, over-the-counter medications, “as needed” medications, vitamins, supplements, and herbal medications. Allergies should also be verified and documented.
    [Show full text]
  • Super Greens
    SUPER GREENS SUPPLEMENT FACTS Serving Size: 1 Scoop (10 g) Servings Per Container: 30 Amount Per Serving % Daily Value Calories 25 Total Carbohydrate 6 g 2%* Dietary Fiber 3 g 12%* Sugars 1 g † Protein <1 g <2%* Organic Super Greens, Sprouts & Prebiotic Fiber Blend: 3.5 g Wheat grass, barley grass, spirulina (blue green algae), green pea fiber, oat fiber, flaxseed, blue agave inulin, plum, orange peel, apple fiber, lemon peel, kale, broccoli, spinach, parsley, green cabbage, alfalfa grass, chlorella, green tea, tomato, sweet potato, pumpkin, dandelion root, collard greens, dulse, adzuki sprout, amaranth sprout, buckwheat sprout, chia sprout, flax sprout, garbanzo bean sprout, lentil bean sprout, millet sprout, pumpkin sprout, quinoa sprout, sesame sprout, sunflower sprout Organic Super Foods & Fruits Blend: 3.5 g Beet root, carrot, Organic Berry Blend [acai berry (Euterpe oleracea), apple, banana, bilberry, black currant, blueberry, cherry, elderberry, goji berry (Lycium barbarum), grape, maqui berry (Aristotelia chilensis), papaya, pineapple, pomegranate, raspberry, strawberry], apple, shitake mushroom, reishi mushroom, maitake mushroom, blueberry, raspberry, strawberry, peach, blackberry, lemon, pear, cranberry, grape, pomegranate, cherry, orange Probiotic Blend: 500 million CFU Bacillus coagulans, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei, Streptococcus thermophilus * Percent Daily Values are based on a 2,000 calorie diet. † Daily value not established. Other ingredients: Organic tapioca starch, organic guar gum, citric acid, organic natural berry flavor and organic rebaudioside A. .
    [Show full text]
  • AFS – Advances in Food Sciences Continuation of CMTL Founded by F
    AFS – Advances in Food Sciences Continuation of CMTL founded by F. Drawert Production by PSP – Parlar Scientific Publications, Angerstr. 12, 85354 Freising, Germany in cooperation with Lehrstuhl für Chemisch-Technische Analyse und Lebensmitteltechnologie, Technische Universität München, 85350 Freising - Weihenstephan, Germany Copyright © by PSP – Parlar Scientific Publications, Angerstr. 12, 85354 Freising, Germany. All rights are reserved, especially the right to translate into foreign language. No part of the journal may be reproduced in any form- through photocopying, microfilming or other processes- or converted to a machine language, especially for data processing equipment- without the written permission of the publisher. The rights of reproduction by lecture, radio and television transmission, magnetic sound recording or similar means are also reserved. Printed in GERMANY – ISSN 14311431----77377737 © by PSP Volume 24 – No 4. 2002 Advances in Food Sciences 1 © by PSP Volume 24 – No 4. 2002 Advances in Food Sciences AFSAFS---- Editorial Board Chief Editors: Prof. Dr. H. Parlar Institut für Lebensmitteltechnologie und Analytische Chemie, TU München - 85350 Freising-Weihenstephan, Germany - E-mail: [email protected] Dr. G. Leupold Institut für Lebensmitteltechnologie und Analytische Chemie, TU München - 85350 Freising-Weihenstephan, Germany - E-mail: [email protected] CoCo----Editor:Editor: Prof. Dr. R. G. Berger Zentrum Angewandte Chemie, Institut für Lebensmittelchemie, Universität Hannover Wunstorfer Straße 14, 30453 Hannover - E-mail: [email protected] AFSAFS- Advisory Board E. Anklam, I M. Bahadir, D F. Coulston, USA J.M. de Man, CAN N. Fischer, D S. Gäb, D A. Görg, D U. Gill, CAN D. Hainzl, P W.P. Hammes, D D. Kotzias, I F.
    [Show full text]
  • Public Health Impact a Suitable Test for L-Citrulline—
    1 Winter 2016 Public Health Impact A Suitable Test for L-citrulline— How Validated Test Methods May New Dietary Supplements Impact Public Health Reference Standards In the U.S., most newborn babies are screened for rare inborn errors of Below is a list of newly released metabolism (IEM)—a group of genetic disorders caused by a defect in a reference standards: metabolic pathway. Left untreated, these disorders can lead to a host of Botanicals medical and developmental consequences ranging from intellectual 1 disability to severe cognitive impairment and even death. • 2,3,5,4’-Tetrahydroxystilbebe-2- Some of these metabolic errors require the use of amino acids to avoid O-Beta-D-Glucoside the buildup of ammonia in the body. L-citrulline is one such amino acid, • Emodin and it is used for IEM as a medical food, which is regulated by the U.S. Food and Drug Administration (FDA) under the Orphan Drug Act. Medical • Polygonum multiflorum Root Dry foods are distinct within the broader category of foods and need to be Extract administered under the supervision of a healthcare professional • Lonicera japonica Flower Dry specifically to help manage a disease or condition associated with Extract distinctive nutritional requirements. In addition to being marketed as a medical food for IEM, L-citrulline is marketed as a dietary supplement for • Secoxyloganin other purposes. • Lonicera macranthoides Flower Sometimes, the quality control testing done to authenticate ingredients is Dry Extract insufficient to guarantee their quality. That was the case with L-citrulline in Luteolin-7-O-glucoside 2014. • One of the primary suppliers of the ingredient for use as a medical food voluntarily recalled several batches of the product after the FDA warned Non-Botanicals that the product being sold had no L-citrulline present.
    [Show full text]
  • Dietary Supplements Compendium Volume 1
    2015 Dietary Supplements Compendium DSC Volume 1 General Notices and Requirements USP–NF General Chapters USP–NF Dietary Supplement Monographs USP–NF Excipient Monographs FCC General Provisions FCC Monographs FCC Identity Standards FCC Appendices Reagents, Indicators, and Solutions Reference Tables DSC217M_DSCVol1_Title_2015-01_V3.indd 1 2/2/15 12:18 PM 2 Notice and Warning Concerning U.S. Patent or Trademark Rights The inclusion in the USP Dietary Supplements Compendium of a monograph on any dietary supplement in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grant of, or authority to exercise, any right or privilege protected by such patent or trademark. All such rights and privileges are vested in the patent or trademark owner, and no other person may exercise the same without express permission, authority, or license secured from such patent or trademark owner. Concerning Use of the USP Dietary Supplements Compendium Attention is called to the fact that USP Dietary Supplements Compendium text is fully copyrighted. Authors and others wishing to use portions of the text should request permission to do so from the Legal Department of the United States Pharmacopeial Convention. Copyright © 2015 The United States Pharmacopeial Convention ISBN: 978-1-936424-41-2 12601 Twinbrook Parkway, Rockville, MD 20852 All rights reserved. DSC Contents iii Contents USP Dietary Supplements Compendium Volume 1 Volume 2 Members . v. Preface . v Mission and Preface . 1 Dietary Supplements Admission Evaluations . 1. General Notices and Requirements . 9 USP Dietary Supplement Verification Program . .205 USP–NF General Chapters . 25 Dietary Supplements Regulatory USP–NF Dietary Supplement Monographs .
    [Show full text]
  • Potential Use of Bacillus Coagulans in the Food Industry
    foods Review Potential Use of Bacillus coagulans in the Food Industry Gözde Konuray * ID and Zerrin Erginkaya ID Department of Food Engineering, Cukurova University, Adana 01330, Turkey; [email protected] * Correspondence: [email protected]; Tel.: +90-322-338-60-84 Received: 1 May 2018; Accepted: 11 June 2018; Published: 13 June 2018 Abstract: Probiotic microorganisms are generally considered to beneficially affect host health when used in adequate amounts. Although generally used in dairy products, they are also widely used in various commercial food products such as fermented meats, cereals, baby foods, fruit juices, and ice creams. Among lactic acid bacteria, Lactobacillus and Bifidobacterium are the most commonly used bacteria in probiotic foods, but they are not resistant to heat treatment. Probiotic food diversity is expected to be greater with the use of probiotics, which are resistant to heat treatment and gastrointestinal system conditions. Bacillus coagulans (B. coagulans) has recently attracted the attention of researchers and food manufacturers, as it exhibits characteristics of both the Bacillus and Lactobacillus genera. B. coagulans is a spore-forming bacterium which is resistant to high temperatures with its probiotic activity. In addition, a large number of studies have been carried out on the low-cost microbial production of industrially valuable products such as lactic acid and various enzymes of B. coagulans which have been used in food production. In this review, the importance of B. coagulans in food industry is discussed. Moreover, some studies on B. coagulans products and the use of B. coagulans as a probiotic in food products are summarized. Keywords: Bacillus coagulans; probiotic; microbial enzyme 1.
    [Show full text]
  • Isolation and Characterization of Probiotic Bacillus Subtilis MKHJ 1-1 Possessing L-Asparaginase Activity
    applied sciences Article Isolation and Characterization of Probiotic Bacillus subtilis MKHJ 1-1 Possessing L-Asparaginase Activity Hyeji Lim 1 , Sujin Oh 1 , Sungryul Yu 2 and Misook Kim 1,* 1 Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea; [email protected] (H.L.); [email protected] (S.O.) 2 Department of Clinical Laboratory Science, Semyung University, Jecheon 27136, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-41-550-3494 Abstract: The purpose of this study was to isolate functional Bacillus strains from Korean fermented soybeans and to evaluate their potential as probiotics. The L-asparaginase activity of MKHJ 1-1 was the highest among 162 Bacillus strains. This strain showed nonhemolysis and did not produce β-glucuronidase. Among the nine target bacteria, MKHJ 1-1 inhibited the growth of Escherichia coli, Pseudomonas aeruginosa, Shigella sonnei, Shigella flexneri, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus cereus. 16S rRNA gene sequence analysis resulted in MKHJ 1-1 identified as Bacillus subtilis subsp. stercoris D7XPN1. As a result of measuring the survival rate in 0.1% pepsin solution (pH 2.5) and 0.3% bile salt solution for 3 h, MKHJ 1-1 exhibited high acid resistance and was able to grow in the presence of bile salt. MKHJ 1-1 showed outstanding autoaggregation ability after 24 h. In addition, its coaggregation with pathogens was strong. Therefore, MKHJ 1-1 is a potential probiotic with L-asparaginase activity and without L-glutaminase activity, suggesting that it could be a new resource for use in the food and pharmaceutical industry.
    [Show full text]
  • BIOMEFX RECOMMENDATIONS 2 Dysbiosis Ratios
    REPORT RECOMMENDATIONS 02....................................... ALPHA AND BETADIVERSITY RESISTOME DYSBIOSIS RATIOS Firmicutes: Bacteroidetes, Proteobacteria:Actinobacteria, Prevotella:Bacteroides Ratio 04....................................... PATHOGENS Clostridium dicile, Helicobacter pylori, Campylobacter species: C. concisus, C. showae, C. hominis, C. ureolyticu, Escherichia coli, Salmonella enterica, Yersinia enterocolitica, Klebsiella pneumoniae (opportunistic), Citrobacter freundii, Hafnia alvei (opportunistic), Raoultella ornithinolytica, Bilophila wadsworthia, Vibrio cholerae, Candida species, Geotrichum spp, Microsporidia spp, Rhodotorula spp, Giardia lamblia, Cyclospora cayetanensis, Blastocystis hominis, Cryptosporidium, Entamoeba histolytica, Adenovirus, Cytomegalovirus, Epstein Barr virus 12 ....................................... FUNCTIONS Saccharolytic Fermentation, Butyrate production, Propionate production, Acetate Production, Lactate production, Proteolytic fermentation, Polyamine production, P-cresol production, Ammonia production, Hydrogen Sulfide production, Methane Production, GABA Production, Glutathione production, Indole production, Estrobolome (estrogen recycling), Vitamin Production, Vit B1 Thiamin, Vit B2 Riboflavin, Vit B5 - Pantothenic acid, Vit B6 - Pyridoxine, Vit B7 - Biotin, Vit B9 - Folate, Vit B12 - Cobalamin, Vitamin K2 23....................................... KEYSTONE SPECIES Akkermansia muciniphila, Faecalibacterium prausnitzii, Butyricicoccus pullicaecorum, Ruminococcus bromii, Ruminococcus flavefaciens,
    [Show full text]