Amino Acid Biosynthesis
By Laura Voss
Biosynthesis vs. Metabolism
• Not the same as amino acid metabolism
pathways.
– Synthesis of most amino acids is only one or
two steps removed from another pathway or
cycle.
– Missing genes = metabolites not produced.
Many metabolites are not essential to the cell.
Biosynthesis Pathways
• Valine, leucine, and isoleucine
biosynthesis
– Essential pathways complete
• Lysine biosynthesis
– Essential genes missing
• Phenylalanine, tyrosine, and tryptophan
biosynthesis
– Essential genes missing
Valine, Leucine, and Isoleucine
• One missing gene: 2.3.1.182, (R)-citramalate synthase
Found
• (R)-citramalate synthase found by name in
JGI and Manatee, not RAST
– Run BLAST for amino acid sequences from
JGI and Manatee on RAST
• Recognizes amino acid sequences but ID’s them
as isopropylmalate synthase – same COG as
citramalate synthase.
Lysine
Lysine – missing genes
• One “cluster” of genes missing
• Either 1.4.1.6 or 5.1.1.7 must be present
• Neither appear in any of the databases
– Searching for parts of their names brings up
nonspecific similar compounds, which H.
utahensis might use to work around the
missing genes.
– Many genes don’t appear in H. marismortui
either.
Phenylalanine, Tyrosine, and Tryptophan
Missing Genes:
• 4.2.3.4 (3-dehydroquinate synthase)
– Found, via name search, in all 3 databases
• 5.4.99.5 (Chorismate mutase)
– Found, with E.C. Number intact, in JGI and
Manatee; E.C. number not in RAST.
• 2.5.1.54 (3-deoxy-7-phosphoheptulonate
synthase or DHAP synthase)
– Not found in any database or in BLASTer
search!)
•EXPASY tags as DHAP
synthase.
•Searching for DHAP
synthase in Pfam and
other protein databases
gives no result.
•Redirects to DHAP
synthetase, class I –
also not found.
•Also missing in H.
marismortui KEGG.
Conclusions and Remaining
Questions:
• Valine, leucine, and isoleucine complete as they
appear on KEGG
• Lysine does not, but alternative proteins may be
present, allowing a way around missing genes.
• Phenylalanine, tyrosine, and tryptophan are
incomplete; no obvious substitute proteins, plus
2.5.1.54’s absense from Pfam.
– Possibility: Use HMM Logo for DHAP synthetase?