While trying to use MEGAN5 recently (version 5.11.3) noticed that most genes were not being mapped to KEGG/SEED categories. Turns out that the built-in reference maps for KEGG and SEED are now out-of date and you need to supply auxiliary mapping files when importing from a blastp file (blasted using recently updated versions of NCBI’s nr database), they can be found here: http://ab.inf.uni-tuebingen.de/data/software/megan5/download/welcome.html
For these mapping files to work however you need GI numbers in your blastp file. BLAST does not automatically include NCBI’s GI numbers when performing searches on command-line, but their inclusion can be specified by the argument “-show_gis”. Don’t know of an easy way to introduce GI numbers post-BLAST search; probably easiest to redo any that don’t include them if you want to view output with MEGAN5.
So if you notice that when using MEGAN recently that few of your genes have KEGG or SEED hits this could be why!