Stephane B. Richard

MEDIT SA (Molecular Extended Distribution in Information Technology) is a privately held software editor company operating in the Saclay Scientipole area, France, and in the process of expending its activities in the US.
MEDIT SA efforts are focused on using structural experimental data from the PDB as the guideline for drug design (Both lead identification and lead optimization). Our core technology MED-SuMo is a new high speed, accurate and innovative chemogenomic solution for Structure Based Drug Design (SBDD) offered to crystallographers, molecular modelers and medicinal chemists.

French BioBeach is a San Diego based Biotech Networking Organization collaborating with French development agencies and both French and US based Biotech companies and academic institutions to put together transatlantic partnerships and collaborations as well as helping the creation of French funded biotech from US based scientific IP.

1. Biochemistry
2. Molecular Biology
3. Chemical Biology
4. Metabolic Engineering
5. Biotechnology
6. X-ray crystallography
7. Protein Purification
8. Drug Design
9. Structural Biology
10. International Business
11. Crystallography
12. Site-directed Mutagenesis
13. Affinity Chromatography

• French

  (Native or bilingual proficiency)

• English

  (Native or bilingual proficiency)

• Spanish

  (Elementary proficiency)

• Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products

  • Nature
  • June 16, 2005
  Authors: Stephane B. Richard, Joseph P. Noel, Tomohisa Kuzuyama

  The anti-oxidant naphterpin is a natural product containing a polyketide-based aromatic core with an attached 10-carbon geranyl group derived from isoprenoid (terpene) metabolism1, 2, 3. Hybrid natural products such as naphterpin that contain 5-carbon (dimethylallyl), 10-carbon (geranyl) or 15-carbon (farnesyl) isoprenoid chains possess biological activities distinct from their non-prenylated aromatic precursors4. These hybrid natural products represent new anti-microbial, anti-oxidant, anti-inflammatory, anti-viral and anti-cancer compounds. A small number of aromatic prenyltransferases (PTases) responsible for prenyl group attachment have only recently been isolated and characterized5, 6. Here we report the gene identification, biochemical characterization and high-resolution X-ray crystal structures of an architecturally novel aromatic PTase, Orf2 from Streptomyces sp. strain CL190, with substrates and substrate analogues bound. In vivo, Orf2 attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide during naphterpin biosynthesis. In vitro, Orf2 catalyses carbon–carbon-based and carbon–oxygen-based prenylation of a diverse collection of hydroxyl-containing aromatic acceptors of synthetic, microbial and plant origin. These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases.

• SR's Peer Reviewed Papers

  Authors: Stephane B. Richard

• Method of screening inhibitors of mevalonate-independent isoprenoid biosynthetic pathway

  • United States Patent PCT/US2001/014371
  • Issued May 3, 2000
  Inventors: Stephane B. Richard, Joseph P. Noel, Marianne E. Bowman

  The present invention provides the structure of the enzyme 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) synthase, a member of the cytidyltransferase family of enzymes from Escherichia coli. CDP-ME is a critical intermediate in the mevalonate-independent pathway for isoprenoid biosynthesis in a number of prokaryotic organisms, in algae, in the plastids of plants, and in the malaria parasite. Since vertebrates synthesize isoprenoid precursors using a mevalonate pathway, CDP-ME synthase and other enzymes of the mevalonate-independent pathway for isoprenoid production represent attractive targets for the structure-based design of selective antibacterial, herbicidal, and antimalarial drugs. Accordingly, the present invention provides methods for screening for compounds that inhibit enzymes of the mevalonate-independent pathway and pharmaceutical compositions and antibacterial formulations thereof. Further provided are methods of inhibiting the enzymes of the pathway and bacterial terpenoid synthesis and methods for treating a subject suffering from a bacterial infection.

• Novel Aromatic Prenyltransferases, Nucleic Acids Encoding Same and Uses Therefor

  • United States Patent PCT/US2006/003161
  • Issued January 28, 2005
  Inventors: Stephane B. Richard, Joseph P. Noel, Tomohisa Kuzuyama

  A bacterial enzyme that transfers a prenyl group to an aromatic natural product may provide a general biosynthetic route to regioselective prenylation of aromatic small molecules.
  
  Many bioactive natural products contain isoprenoid chains of various lengths, collectively known as prenyl groups. New research has revealed biochemical and structural characterization of Orf2, a prenyltransferase enzyme that attaches a 10-carbon prenyl group to a polyketide during the biosynthesis of the antioxidant naphterpin. This enzyme has a novel barrellike architecture and is unexpectedly promiscuous. In vitro, Orf2 can regiospecifically prenylate a diverse collection of hydroxyl-containing aromatic molecules of microbial, plant, and synthetic origin.
  
  New information on the factors that control which prenyl chain is used and where it's appended on the substrate should guide the design of modified enzymes that can be used to alter the activity of natural products in bacteria, fungi, plants, and animals. This makes it possible to make rare prenylated natural products; and to carry out regioselective prenylation of aromatic chemicals.

• Metabolic engineering of lipid metabolism by improving fatty acid binding and transport

  • United States Patent Application International Patent Application published as WO 2008/008467
  • Filed July 13, 2007
  Inventors: Stephane B. Richard, Florence Pojer, Joseph P. Noel, Elise Larsen, Marianne Bowman

  In addition to their importance in human nutrition, plant fatty acids, or vegetable oils, are major ingredients of nonfood products such as soaps, detergents, lubricants, biofuels, cosmetics, and paints. With the accelerating costs of petroleum, vegetable oils provide an increasingly cost-effective alternate source for raw materials. Yet, though selecting plants for increased oil production by classical methods has been ongoing for at least a century, it has proved difficult and complex to determine trait-genotype associations for this seemingly simple trait.
  
  In plants, the majority of fatty acids are biosynthesized in the plastid. Nearly all aspects of fatty acid metabolism in plants have been uncovered, but one of the remaining questions that has thus far resisted elucidation is how free fatty acids are transferred from an inner thylakoid membrane to an outer envelope of a plastid.
  
  Salk researchers have overcome these difficulties through isolating a family of chalcone isomerase (CHI)-like genes encoding fatty acid binding proteins that assist in transport of fatty acids to the outer plastid envelope, providing a target for engineering lipid metabolism in plants. For example, lipid production is likely to be increased by overexpressing CHI-like fatty acid binding proteins in cells of the plants.
  
  The complete crystal structures of two proteins are described, making it possible to engineer the proteins to modulate fatty acid binding and plastid transport, for example, to increase transport activity. Also provided are CHI-like fatty acid binding proteins and genes, recombinant cells and organisms, methods of metabolic pathway engineering to improve lipid production in cells, and methods and systems of engineering CHI-like fatty acid binding proteins.

• Engineering salt tolerance in photosynthetic microorganisms

  • United States Patent Application PCT/US2010/027039
  • Filed March 11, 2009
  Inventors: Stephane B. Richard, Mike Mendez, Su-Chiung Fang

  Provided herein are compositions and methods for engineering salt tolerance and producing products by photosynthetic organisms. The photosynthetic organisms can be genetically modified to be salt tolerant as compared to an unmodified organism and to produce useful products. The methods and compositions of the disclosure are useful in many therapeutic and industrial applications.

Sites web :

• MEDIT SA
• French BioBeach
• The Salk Institute, La Jolla

Groupes et associations :

2006-Present Founder of French Bio Beach 2007 Board Member, San Diego French American Chamber of Commerce 2005-present Member of San Diego French American Chamber of Commerce 2005-Present Elected member of the Stanford Synchrotron Radiation Laboratory User Office Executive Comittee

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  Academics at the Salk Institute
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  Alumni from the Salk Institute
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  BIOCOM
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  Biotech & Pharma Professionals Network
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  CCEF in the USA
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  CONNECT
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  Conseillers du Commerce Extérieur de la France (CCEF)
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  French American Chamber of Commerce, New England Chapter
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  French BioBeach
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  Informatics and IT for Life Sciences Group
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  Jobs in computational chemistry, computational drug design, cheminformatics & molecular modeling
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  Structure-Based Drug Design
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  Symposium mondial des CCE 2012
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  TVG - Your Global Life Science Network

Distinctions et prix :

AWARDS:
2005 Spicer Young Investigator Award of the Stanford Synchrotron Facility (SSRL)
2003 Salk Science Day Award organized by the SRF association
2001 Scientific exchange fellowship, Philippe Foundation Inc. (New York, Paris)
1995-98 CFR fellowship, French Atomic Energy Commission (CEA, France)