*3.3. Phylogenetic Analysis of CYP128 P450s*

Phylogenetic analysis of CYP128 P450s was carried out following the method described elsewhere [31]. First, the protein sequences were aligned by MAFFT v6.864 embedded on the Trex web server [48]. Thereafter, the alignments were automatically subjected to tree inferring and optimization by the Trex web server [49]. Finally, the best-inferred tree was envisioned and colored using iTOL (http://itol.embl.de/about.cgi) [50].

#### *3.4. Amino Acid Conservation Analysis*

Amino acid conservation analysis of CYP128 P450s was carried out following the methods described elsewhere [22,31,32]. Briefly, 2191 CYP128 P450s with amino acid length ranging from 475–496 amino acids (Supplementary Dataset 1) were selected and subjected to PROMALS3D analysis [33]. In order to calculate the accurate number of conserved amino acids in P450s, it was mentioned that P450s with similar amino acid length should be used [22,25,31,32]. PROMALS3D analysis provided the amino acid conservation index at different protein sequence positions [33], using the numbers from 5 to 9, where 9 is the invariantly conserved amino acid. The conserved number of amino acids for each conservation index was counted and compared with other P450 families from different biological kingdoms [22,25,31,32] to determine the CYP128 P450 family conservation rank.

#### *3.5. Generation of EXXR and CXG Sequence Logos*

CYP128 P450 family EXXR and CXG sequence logos were constructed using the method described elsewhere [22,32,34]. Briefly, all CYP128 P450 sequences were aligned using ClustalW multiple alignments embedded in MEGA7 [51]. Then the EXXR and CXG region amino acids (4 and 10 amino acids, respectively), were copied and pasted in the WebLogo program (http://weblogo.berkeley.edu/ logo.cgi) [52,53]. As a selection parameter, the image format was selected as PNG (bitmap) at 300 dpi resolution. The percentage predominance of amino acids at specific positions was calculated, taking into account the total number of amino acids as 100%. The generated EXXR and CXG logos were used for analysis and comparison to the different P450 family EXXR and CXG logos that have been published and are accessible to the public [22,31,32,34].
