ID   HKM3_ASPHA              Reviewed;         484 AA.
AC   P0DUL1;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   02-JUN-2021, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=O-acetyltransferase hkm3 {ECO:0000303|PubMed:33242032};
DE            EC=2.3.1.- {ECO:0000269|PubMed:33242032};
DE   AltName: Full=Hancockiamides biosynthesis cluster protein 3 {ECO:0000303|PubMed:33242032};
OS   Aspergillus hancockii.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=1873369;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FRR 3425 / CBS 142004 / DTO 360-G7;
RA   Gilchrist C.L.M., Chooi Y.H.;
RL   Submitted (APR-2019) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOTECHNOLOGY.
RX   PubMed=33242032; DOI=10.1039/d0ob02243h;
RA   Li H., Lacey A.E., Shu S., Kalaitzis J.A., Vuong D., Crombie A., Hu J.,
RA   Gilchrist C.L.M., Lacey E., Piggott A.M., Chooi Y.H.;
RT   "Hancockiamides: phenylpropanoid piperazines from Aspergillus hancockii are
RT   biosynthesised by a versatile dual single-module NRPS pathway.";
RL   Org. Biomol. Chem. 19:587-595(2021).
CC   -!- FUNCTION: O-acetyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of hancockiamides, an unusual new family of N-
CC       cinnamoylated piperazines (PubMed:33242032). The NRPS hkm10 and the
CC       NmrA-like reductase hkm9 are proposed to convert two molecules of L-Phe
CC       to the intermediary piperazine called xenocockiamide A (Probable).
CC       Xenocockiamide A is then converted to hancockiamide D via a series of
CC       hydroxylations and O-methylations (Probable). The tyrosinase hkm6 may
CC       catalyze an aromatic hydroxylation, then the 2-oxoglutarate-dependent
CC       Fe(II) dioxygenase hkm4 and the FAD-dependent phenol hydroxylase hkm7
CC       may catalyze consecutive hydroxylations to install 2 more hydroxy
CC       groups, and the methyltransferase hkm8 probably catalyzes two
CC       methylations using 2 molecules of S-adenosyl-L-methionine (SAM)
CC       (Probable). The NRPS hkm11 activates and transfers trans-cinnamate
CC       supplied by the PAL hkm12 to hancockiamide D and produces hancockiamide
CC       A (PubMed:33242032). NRPS Hkm11 has the flexibility to tolerate the
CC       bulky hancockiamide G as a substrate and the absence of the acetyl-
CC       transferase hkm3 opens up the opportunity for hkm11 to introduce a
CC       second N-cinnamoyl moiety (PubMed:33242032). The cytochrome P450
CC       monooxygenase hkm5 catalyzes the methylenedioxy bridge formation,
CC       converting hancockiamide A into hancockiamide G (PubMed:33242032). Hkm5
CC       can also convert hancockiamide B into hancockiamide C, and
CC       hancockiamide D into hancockiamide H (PubMed:33242032). The N-
CC       acetyltransferase hkm3 finally transfers an acetyl group to 1-N of
CC       piperazine, converting hancockiamide A into hancockiamide B and
CC       hancockiamide G into hancockiamide C (PubMed:33242032).
CC       {ECO:0000269|PubMed:33242032, ECO:0000305|PubMed:33242032}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:33242032}.
CC   -!- BIOTECHNOLOGY: Hancockiamide D displays potent cytotoxic activity
CC       against murine myeloma NS-1 cells, suggesting a potential antitumour
CC       application (PubMed:33242032). More interestingly, hancockiamide C, the
CC       likely end metabolite of the hkm pathway, shows potent Arabidopsis
CC       thaliana seed anti-germination activity, but is inactive against the
CC       monocot Eragrostis tef seed, suggesting that it could be a herbicidal
CC       lead targeting monocots (PubMed:33242032). The herbicidal activity of
CC       hancockiamide C could be due to its phenylpropanoid-like structural
CC       features, which may act on the plant lignan pathways, and hence
CC       warrants further investigations (PubMed:33242032).
CC       {ECO:0000269|PubMed:33242032}.
CC   -!- SIMILARITY: Belongs to the fumigaclavine B O-acetyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; MBFL02000005; KAF7597147.1; -; Genomic_DNA.
DR   AlphaFoldDB; P0DUL1; -.
DR   SMR; P0DUL1; -.
DR   GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.559.10; -; 2.
DR   InterPro; IPR023213; CAT-like_dom_sf.
PE   1: Evidence at protein level;
KW   Acyltransferase; Transferase.
FT   CHAIN           1..484
FT                   /note="O-acetyltransferase hkm3"
FT                   /id="PRO_0000452930"
SQ   SEQUENCE   484 AA;  53302 MW;  993443CE0AC3DAD4 CRC64;
     MTKLDSPQFE PFELTAADYA FPMFYAGCTL SFRLKSPEMG IPVLQTAVER ITAHLPFLTG
     IVIPSAVKDG VMEVHPAACG QSGLEDPQCR VRRLPHLCLP PKTASASANK KHGSGMTYDR
     NECLIVAPLE AATAAQQHPV IRFQINVLAD GIIFTLFANH MVIDGTGLGI ITEMLASCCQ
     TADNTGSVPE LAGAIDREAR TRAMLGTIGR REREKVQFEP VAAESAAPDG HQEVHDASLV
     DCNFRLSADK IRRIRERAQE LGIASASEDD IVTAVLWLCM SEFRSHSGAG KEISACTLLR
     MVNVRRRFHP AVPDNYLGNC YIMIEETLPT TDLSGGAAQA STEEDFLRLI GVVASVLRSR
     LNRVDDQYVR DHLAQFTHAG DWAHTTIHEP DVAVTSLRGM SVYSLDFGSV LSGIVDFETL
     PYMNPDGVCT IKPRRVIDPS WEVAVTLSRE DMDRLRKNEL FRWLVVGESY LHIFQSAQQV
     TTFA