Detail Information for IndEnz0016000089
IED ID IndEnz0016000089
Enzyme Type ID tyrosinase000089
Protein Name Nonribosomal peptide synthetase hkm11
EC 6.3.2.-
Hancockiamides biosynthesis cluster protein 11
Gene Name
Organism Aspergillus hancockii
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus hancockii
Enzyme Sequence MTVPATTKDPRDSLLDSPLVHFPSLPRDSYLPHPTEHTVVSIDDEEILPSTRSSLHDVLQVAWSLVLADQTSSPEVVFGMAYDGRTTDDGEQAIMPFRLRLRAEDSVQEALAAAAAVTLQMRQWEHMGLRRFSTMSPQNVVLCQFRNLFVIDHKDPTEDCVERSCTSYSKGYALTVLCEIVDQVIHVHAMFDPLVLPPGQLRLILHQFGDILKTCLRGPPGRVKDLQQIGPDGLNYIYEWNRGGERDEGIVCVHQLIEDRFKQAPFAAAVCAWDGALTYGELDRWAKRIAAQLVEAGVKPGSFVGIYMQKSVLAVVAMVAIVKAGAAFIFLPPFLPTVRLQLMCQRTPVELVLSVATLLRSASDLSVPVQVLDYRAKDEEETAATSGGSEIAQPNHPLYAIFTSGSTGEPKGVVVDRASFGPGVREYCRRAQLGPNSRLFQSVSYAFIVSIFEQLISLALGACICVPSEEQLQNDMEGAMCRYQATWGCMTPSVARTLKPERLSCLKTLALTGEPVNQSDMEQWKDHVNLYTLYGQSETGSTLLINSITGSLADSRGLGRPSTGACWIVDPEDPTTLRPLGAEGELLIETTALARGYMNNLEESARTFIEMPKWLKQLRPQGHRSRCLLTGDIVRYYDTDGTIRLLSRKGTGAKIRGQRVELGEIEHHLRPKFPDARHILVDVVCPAKAGTGHSILVAFVHGPWKDTEKTGELATATSEFRQQARRVIAELRQVLPSFMVPSAIVPLADVPTTATGKVHRKSLRERMSALTVAEILAYNQEDRSAYRAPTTEQEALLLSICAELLYLPASSISLDNSFFQVGGDSLNARQLAAKVRSHGFSLLATDIFEASTLASLASRMRQYNQTDSEVSTAPEGDPFEGLKQELLGELPSSLVKENVEDVYPASDMQARAIRTHMLDYFPFEIKGQLDRHQLQHACETLIRRTPVMRSVFINFRGKMLQVTLRSVAIPYKELTIPTGEDPLSWARLHIAEDKKKTAAFDRPTIRFTLCRQSLQHHIFIVRLPHAIYDGSCLEQVAKQISAAYNAQTLPEAPDFAAYARRCARLRTPSAMDFWRNFLAESEVTRLPHASKGDEVAVIYPGECSPRSPPPGITMATAIKAAWAWVLHKRTGKLDVLFGQVGSTRGIDIPGATDIIGLCLNITAVRVQFAGLQTVEDLLRMLQQQHMRALMYETADWTDIVANASSWPEGTELDSVVLHENFGGLPALDLGDAIGEMADPIFSLSTSNPLTLVTWPSTQTLTSFLLTRENVFQKEYAEGLVTEFNQTLVQFLDFPESSLCSISTCG
Enzyme Length 1305
Uniprot Accession Number P0DUL9
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number 6.3.2.-
Enzyme Function FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of hancockiamides, an unusual new family of N-cinnamoylated piperazines (PubMed:33242032). The NRPS hkm10 and the NmrA-like reductase hkm9 are proposed to convert two molecules of L-Phe to the intermediary piperazine called xenocockiamide A (Probable). Xenocockiamide A is then converted to hancockiamide D via a series of hydroxylations and O-methylations (Probable). The tyrosinase hkm6 may catalyze an aromatic hydroxylation, then the 2-oxoglutarate-dependent Fe(II) dioxygenase hkm4 and the FAD-dependent phenol hydroxylase hkm7 may catalyze consecutive hydroxylations to install 2 more hydroxy groups, and the methyltransferase hkm8 probably catalyzes two methylations using 2 molecules of S-adenosyl-L-methionine (SAM) (Probable). The NRPS hkm11 activates and transfers trans-cinnamate supplied by the PAL hkm12 to hancockiamide D and produces hancockiamide A (PubMed:33242032). NRPS Hkm11 has the flexibility to tolerate the bulky hancockiamide G as a substrate and the absence of the acetyl-transferase hkm3 opens up the opportunity for hkm11 to introduce a second N-cinnamoyl moiety (PubMed:33242032). The cytochrome P450 monooxygenase hkm5 catalyzes the methylenedioxy bridge formation, converting hancockiamide A into hancockiamide G (PubMed:33242032). Hkm5 can also convert hancockiamide B into hancockiamide C, and hancockiamide D into hancockiamide H (PubMed:33242032). The N-acetyltransferase hkm3 finally transfers an acetyl group to 1-N of piperazine, converting hancockiamide A into hancockiamide B and hancockiamide G into hancockiamide C (PubMed:33242032). {ECO:0000269|PubMed:33242032, ECO:0000305|PubMed:33242032}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:33242032}.
nucleotide Binding
Features Chain (1); Domain (1); Modified residue (1); Region (2)
Keywords Ligase;Phosphopantetheine;Phosphoprotein
Interact With
Induction
Subcellular Location
Modified Residue MOD_RES 825; /note=O-(pantetheine 4'-phosphoryl)serine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00258
Post Translational Modification
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID -
Motif
Gene Encoded By
Mass 144,312
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda