FEATURES

FAMILY

DESCRIPTION

Also known as MPAH2_PENBR, mpaH'. Type I acyl-CoA thioesterase; part of the gene cluster that mediates the biosynthesis of mycophenolic acid (MPA), the first isolated antibiotic natural product in the world obtained from a culture of Penicillium brevicompactum in 1893 (PubMed:25630520, PubMed:31209052). The first step of the pathway is the synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic polyketide synthase mpaC' via the condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units and one methylation step (PubMed:31209052). 5MOA is then converted to the phthalide compound 5, 7-dihydroxy-4, 6-dimethylphthalide (DHMP) by the endoplasmic reticulum-bound cytochrome P450 monooxygenase mpaDE' (PubMed:31209052). MpaDE' first catalyzes hydroxylation of 5-MOA to 4, 6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB) (PubMed:31209052). MpaDE' then acts as a lactone synthase that catalyzes the ring closure to convert DHMB into DHMP (PubMed:31209052). The next step is the prenylation of DHMP by the Golgi apparatus-associated prenyltransferase mpaA' to yield farnesyl-DHMP (FDHMP) (PubMed:31209052). The ER-bound oxygenase mpaB' then mediates the oxidative cleavage the C19-C20 double bond in FDHMP to yield FDHMP-3C via a mycophenolic aldehyde intermediate (PubMed:31209052). The O-methyltransferase mpaG' catalyzes the methylation of FDHMP-3C to yield MFDHMP-3C (PubMed:31209052). After the cytosolic methylation of FDHMP-3C, MFDHMP-3C enters into peroxisomes probably via free diffusion due to its low molecular weight (Probable). Upon a peroxisomal CoA ligation reaction, catalyzed by a beta-oxidation component enzyme acyl-CoA ligase ACL891, MFDHMP-3C-CoA would then be restricted to peroxisomes for the following beta-oxidation pathway steps (PubMed:31209052). The peroxisomal beta-oxidation machinery than converts MFDHMP-3C-CoA into MPA_CoA, via a beta-oxidation chain-shortening process (PubMed:31209052). Finally mpaH' acts as a peroxisomal acyl-CoA hydrolase with high substrate specificity toward MPA-CoA to release the final product MPA (PubMed:31209052).

EXTERNAL LINKS

mpaH'

Type I acyl-CoA thioesterase mpaH'

mpaH'

Molecular Synopsis