In microbiome analysis, one main approach is to align metagenomic sequencing reads against a protein-reference database such as NCBI-nr, and then to perform taxonomic and functional binning based on the alignments. This approach is embodied, for example, in the standard DIAMOND+MEGAN analysis pipeline, which first aligns reads against NCBI-nr using DIAMOND and then performs taxonomic and functional binning using MEGAN. Here we propose the use of the AnnoTree protein database, rather than NCBI-nr, in such alignment-based analyses to determine the prokaryotic content of metagenomic samples. We demonstrate a 2-fold speedup over the usage of the prokaryotic part of NCBI-nr, and increased assignment rates, in particular, assigning twice as many reads to KEGG. In addition to binning to the NCBI taxonomy, MEGAN now also bins to the GTDB taxonomy.