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Biochemistry Seminar – Valerie de Crecy-Lagard:”Discovery of 7-deazapurine synthesis pathways: where RNA and DNA modifications intersect with secondary metabolites”

February 21 @ 4:00 pm - 5:00 pm

Dr. Valerie de Crecy-Lagard

Department of Microbiology and Cell Science

University of Florida

Title: “Discovery of 7-deazapurine synthesis pathways: where RNA and DNA modifications intersect with secondary metabolites

Abstract:

        Identifying the function of every gene in all sequenced organisms is the major challenge of the post-genomic era and an obligate step for any syst­ems biology approach. This object­ive is far from reached. By various estimates, at least 30-50% of the genes of any given organism are of unknown function, incorrectly annotated, or have only a generic annotat­ion such as “ATPase”. Moreover, with ~100,000 genomes sequenced (http://www.genomeson.line.org), the numbers of unknown genes are increasing, and annot­at­ion errors are proliferating rapidly. For some gene families, 40% of the annotations are wrong. On the other side of the coin, there are still ~1,900 known enzyme activities for which no corresponding gene has been identified and these numbers are also increasing. This biochemical knowledge is yet to be captured in genome annotations.

       Using mainly a comparative genomic approach, we have linked gene and function for around 50 families related mainly to the fields of coenzyme metabolism, tRNA modification, protein modification and more recently metabolite repair. This approach inte­grates several types of data and uses filters, sieves, and associations to make predictions that can then be tested experimentally. An un­known gene’s function may thus be pre­dicted from those of its associates: the ‘guilt by assoc­iat­ion’ prin­ciple. Assoc­iations that can be de­r­ived from whole gen­ome data­sets incl­ude: gene clustering, gene fusion events, phylogenetic occurrence profiles or signa­tures and shared regulatory sites. Post-genomic experimental sources such as protein inter­action networks, gene expression profiles and phenomics data can also be used to find asso­ciations. In pract­ice it is often ‘guilt by multiple association’ as genes can be ass­­oc­iat­ed in several ways, and analyzing more than one of these impr­oves the accuracy of predict­ions.

         We have applied these methods to decipher the synthesis and salvage pathways for two azapurine modifications of tRNA, Queuosine (Q) and Archaeosine (G+), made from the same precursor molecule PreQ0.  This has led to the discovery of many unforeseen roles for PreQ0 derivatives that will be discussed. These include: 1) the fact that the queuine base is a forgotten vitamin in Eukaryotes that has to be salvaged from the diet or microflora; 2) the discovery of links between Q and metal homeostasis in different kingdoms of life; 3) to the identification of   7-deazapurine in bacterial and phage DNA as well as novel secondary metabolite clusters by miming genomes for novel preQ0 synthesis  gene clusters.

Host: Jorge Cruz-Reyes

Location: 108 Biochemistry Building (Bldg#1507)

Details

Date:
February 21
Time:
4:00 pm - 5:00 pm

Organizer

Jorge Cruz-Reyes

Venue

108 Biochemistry Building (Bldg.#1507)
300 Olsen Blvd
College Station, TX 77845 United States
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