Abstract:
:The study of the metabolome presents numerous challenges, first among them being the cataloging of its constituents. A step in this direction will be the development of tools to identify metabolites that share common structural features. The importance of sulfated molecules in cell-cell communication motivated us to develop a rapid two-step method for identifying these metabolites in microorganisms, particularly in pathogenic mycobacteria. Sulfurcontaining molecules were initially identified by mass spectral analysis of cell extracts from bacteria labeled metabolically with a stable sulfur isotope (34SO 4 2-). To differentiate sulfated from reduced-sulfur-containing molecules, we employed a mutant lacking the reductive branch of the sulfate assimilation pathway. In these sulfur auxotrophs, heavy sulfate is channeled exclusively into sulfated metabolites. The method was applied to the discovery of several new sulfated molecules in Mycobacterium tuberculosis and Mycobacterium smegmatis. Because a sulfur auxotrophic strain is the only requirement of the approach, many microorganisms can be studied in this manner. Such genetic engineering in combination with stable isotopic labeling can be applied to various metabolic pathways and their products.
journal_name
Proc Natl Acad Sci U S Aauthors
Mougous JD,Leavell MD,Senaratne RH,Leigh CD,Williams SJ,Riley LW,Leary JA,Bertozzi CRdoi
10.1073/pnas.252514899keywords:
subject
Has Abstractpub_date
2002-12-24 00:00:00pages
17037-42issue
26eissn
0027-8424issn
1091-6490pii
252514899journal_volume
99pub_type
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