Function
Part of the gene cluster that mediates the biosynthesis of pneumocandins, lipohexapeptides of the echinocandin family that prevent fungal cell wall formation by non-competitive inhibition of beta-1,3-glucan synthase (PubMed:27705900). The 10,12-dimethylmyristoyl side chain is synthesized by the reducing polyketide synthase gloL/GLPKS4 (PubMed:27494047). The thioesterase gloN/GLHYD exclusively interacts with gloL/GLPKS4 to maintain turnover of the polyketide side chain (PubMed:27494047). The 10R,12S-dimethylmyristic acid is then transferred to the first thiolation domain of the nonribosomal peptide synthetase gloA/GLNRPS4 by the acyl-AMP ligase gloD/GLligase, followed by its acylation to L-ornithine to trigger elongation of the cyclic hexapeptide (PubMed:27494047). L-ornithine, 4R-hydroxyl-L-proline (generated from L-proline by the dioxygenase gloF/GLOXY2), 3S-hydroxyl-L-homotyrosine (generated by gloG/GLHtyB, gloH/GLHtyA, gloI/GLHtyC, gloJ/GLHtyD and hydroxylated at C-3 by the dioxygenase gloM/GLOXY1), 3R-hydroxyl-L-glutamine (generated from L-glutamine probably by the dioxygenase gloE/GLOXY3) and 3S-hydroxyl-L-proline (generated from L-proline by the dioxygenase gloF/GLOXY2 to yield pneumocandin B0), or 3S-hydroxyl-4S-methyl-L-proline (generated from L-leucine by the dioxygenase gloC/GLOXY4 to yield pneumocandin A0) are sequentially added to the growing chain (PubMed:25270390, PubMed:25879325, PubMed:25527531). The last C domain of gloA/GLNRPS4 is proposed to be responsible for cyclization by condensation to form the peptide bond between L-ornithine and 3S-hydroxyl-4S-methyl-L-proline (for pneumocandin A0) or 3S-hydroxyl-L-proline (for pneumocandin B0). Finally, the subsequent C-4 hydroxylation of 3S-hydroxyl-L-homotyrosine and L-ornithine dihydroxylation at C-4 and C-5 are performed by the cytochrome P450 monooxygenases gloP/GLP450-1 and gloO/GLP450-2, respectively (PubMed:25879325).
Sequence
MDLFQSPGGDLIQDEDSVEVIEMLCIDFRDRLLVALSTTCQSDFREAKKVVEERLRDILETASSLSSTEVTSSPNASPLYNTDAPEDVVPTVGLDVGLDEPMADYSQNTPSITGGTASAEYQNSGDTNQMTLEDPACVDMFAAESQNTGHIPDSCLRDWSFEGVSMKSPSLFDWSSRNSNFPLTQEHENQFAEFLTLFEGEPNFDNWLSTMTWSSLESHSSPINGHSAGATPQLDQMHTVSNSRVARSVVSESTVTNTGSANSLNSGLLANTPSSSHSSVFERACSSVQEPTPEPTPVRGLQRKLRKQGPRQTTEATPCDQQIGPRASRATSQLPERRSMKMVRKEARDTPLTTSPANSTQINIEANTIPSDLSVEYAFGCFSDAKEVFETFYKRLSDDRKHLSSLLMRLFYAVGSPDALRQLRDALDLSRKNSMIASYHDSNDLAATVSVLDQLDATTTLSHILRRYHLVRLLDHRSKLESNHKAAKLAVKGTKRRLKYDCERIELMRRGENADCDANTRSAKERLKYRSKTRALTDLMQTLYPDLSPDSEGITTAGGCEYTRKLTKLRNRLACARNWYQFEETFPGAILALIPCATGDLSISIDHVEKLPSDVLKIFLDYLKERRGVFLSKMSRILSKDLYDVLMRRNVTKRYKLEQTNENSLTDGLHDDDRLLELCETV