The biosynthesis of cysteine and homocysteine in Methanococcus jannaschii

The pathway for the biosynthesis of cysteine and homocysteine in Methanococcus jannaschii has been examined using a gas chromatography-mass spectrometry (GC-MS) stable isotope dilution method to identify and quantitate the intermediates in the pathways. The first step in the pathway, and the one responsible for incorporation of sulfur into both cysteine and methionine, is the reaction between O-phosphohomoserine and a presently unidentified sulfur source present in cell extracts, to produce L-homocysteine. This sulfur source was shown not to be sulfide. The resulting L-homocysteine then reacts with O-phosphoserine to form L-cystathionine, which is cleaved to L-cysteine. The pathway has elements of both the plant and mammalian pathways in that the sulfur is first incorporated into homocysteine using O-phosphohomoserine as the acceptor and the resulting homocysteine, via transsulfuration, supplies the sulfur for cysteine formation. The pathway leading to these two amino acids represents an example of metabolic thrift where the preexisting cellular metabolites O-phosphohomoserine and O-phosphoserine are used as the ultimate source of the carbon framework for the biosynthesis of these amino acids. These findings explain the absence of identifiable genes in the genome of this organism for the biosynthesis of cysteine and homocysteine. (C) 2003 Elsevier B.V. All rights reserved.