fasn-1 (P91871) catalytic-residue conservation vs human FASN (P49327)

Script: catalytic_residues.py (global BLOSUM62 alignment, Biopython PairwiseAligner;
inputs are the cached UniProt flat files genes/worm/fasn-1/fasn-1-uniprot.txt and
genes/human/FASN/FASN-uniprot.txt). Raw output: catalytic_residues_output.tsv.

Run: uv run python genes/worm/fasn-1/fasn-1-bioinformatics/catalytic_residues.py

Result

Global alignment: 2446 aligned residue pairs, 1103 identical (45.1% of aligned pairs);
worm FASN-1 is 2613 aa, human FASN 2511 aa.
Every catalytic residue annotated on human FASN (UniProt ACT_SITE) and the ACP
phosphopantetheine-attachment serine (MOD_RES) aligns to an identical residue in FASN-1:

Human FASN residue	Role	FASN-1 residue
Cys161	beta-ketoacyl synthase (KS)	Cys197
His293	KS	His329
His331	KS	His367
Ser581	malonyl/acetyl transferase (MAT)	Ser621
His878	dehydratase (DH) proton acceptor	His926
Asp1031	DH proton donor	Asp1078
Ser2156	ACP O-(pantetheine 4'-phosphoryl)serine	Ser2248
Ser2308	thioesterase (TE)	Ser2415
His2481	TE	His2591

The worm positions Cys197, His926, Asp1078 and Ser2248 match the positions independently
annotated on P91871 by PROSITE ProRules (KS active site, DH proton acceptor/donor, and
pantetheine-phosphoserine), which is a cross-check that the alignment is in register.

Interpretation

FASN-1 retains the full catalytic toolkit of an animal type I fatty acid synthase:
KS, MAT, DH, ACP and TE catalytic residues are all conserved. The ketoreductase (KR)
and enoylreductase (ER) domains are present by domain signatures (Pfam PF08659 KR,
SMART SM00829 PKS_ER, InterPro IPR020843 ER), but human FASN carries no ACT_SITE
features for KR/ER, so their catalytic residues were not tested here. Nothing in this
analysis suggests loss of any partial activity.