ID   Q93NW7_9ACTN            Unreviewed;      3190 AA.
AC   Q93NW7;
DT   01-DEC-2001, integrated into UniProtKB/TrEMBL.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 136.
DE   SubName: Full=AmphB {ECO:0000313|EMBL:AAK73513.1};
GN   Name=amphB {ECO:0000313|EMBL:AAK73513.1};
OS   Streptomyces nodosus.
OC   Bacteria; Actinomycetota; Actinomycetes; Kitasatosporales;
OC   Streptomycetaceae; Streptomyces.
OX   NCBI_TaxID=40318 {ECO:0000313|EMBL:AAK73513.1};
RN   [1] {ECO:0000313|EMBL:AAK73513.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=11451671; DOI=10.1016/S1074-5521(01)00046-1;
RA   Caffrey P., Lynch S., Flood E., Finnan S., Oliynyk M.;
RT   "Amphotericin biosynthesis in Streptomyces nodosus: deductions from
RT   analysis of polyketide synthase and late genes.";
RL   Chem. Biol. 8:713-723(2001).
RN   [2] {ECO:0000313|EMBL:AAK73513.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=16079135; DOI=10.1074/jbc.M506689200;
RA   Carmody M., Murphy B., Byrne B., Power P., Rai D., Rawlings B., Caffrey P.;
RT   "Biosynthesis of amphotericin derivatives lacking exocyclic carboxyl
RT   groups.";
RL   J. Biol. Chem. 280:34420-34426(2005).
RN   [3] {ECO:0007829|PDB:3MJC, ECO:0007829|PDB:3MJE}
RP   X-RAY CRYSTALLOGRAPHY (1.36 ANGSTROMS) OF 2529-3003 IN COMPLEX WITH NADPH.
RX   PubMed=20696392; DOI=10.1016/j.str.2010.04.015;
RA   Zheng J., Taylor C.A., Piasecki S.K., Keatinge-Clay A.T.;
RT   "Structural and functional analysis of A-type ketoreductases from the
RT   amphotericin modular polyketide synthase.";
RL   Structure 18:913-922(2010).
RN   [4] {ECO:0007829|PDB:4DIF}
RP   X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 2529-3003 IN COMPLEX WITH NADPH.
RA   Zheng J., Keatinge-Clay A.T.;
RT   "Structure and mutagenesis of A2-type ketoreductase from modular polyketide
RT   synthase reveals insights into stereospecificity.";
RL   Submitted (JAN-2012) to the PDB data bank.
RN   [5] {ECO:0007829|PDB:5XWV, ECO:0007829|PDB:5XWW}
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2529-3003 IN COMPLEX WITH NADP(+)
RP   AND NADPH.
RX   PubMed=29626512; DOI=10.1016/j.jsb.2018.04.001;
RA   Liu C., Yuan M., Xu X., Wang L., Keatinge-Clay A.T., Deng Z., Lin S.,
RA   Zheng J.;
RT   "Substrate-bound structures of a ketoreductase from amphotericin modular
RT   polyketide synthase.";
RL   J. Struct. Biol. 203:135-141(2018).
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000256|ARBA:ARBA00001957};
CC   -!- INTERACTION:
CC       Q93NW7; Q93NW7: amphB; NbExp=2; IntAct=EBI-15868936, EBI-15868936;
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DR   EMBL; AF357202; AAK73513.1; -; Genomic_DNA.
DR   PDB; 3MJC; X-ray; 1.48 A; A/B=2529-3003.
DR   PDB; 3MJE; X-ray; 1.36 A; A/B=2529-3003.
DR   PDB; 3MJS; X-ray; 1.40 A; A/B=2529-3003.
DR   PDB; 3MJT; X-ray; 1.60 A; A/B=2529-3003.
DR   PDB; 3MJV; X-ray; 1.46 A; A/B=2529-3003.
DR   PDB; 4DIF; X-ray; 1.52 A; A/B=2529-3003.
DR   PDB; 5XWV; X-ray; 1.80 A; A/B=2529-3003.
DR   PDB; 5XWW; X-ray; 1.96 A; A/B=2529-3003.
DR   PDBsum; 3MJC; -.
DR   PDBsum; 3MJE; -.
DR   PDBsum; 3MJS; -.
DR   PDBsum; 3MJT; -.
DR   PDBsum; 3MJV; -.
DR   PDBsum; 4DIF; -.
DR   PDBsum; 5XWV; -.
DR   PDBsum; 5XWW; -.
DR   SMR; Q93NW7; -.
DR   DIP; DIP-59008N; -.
DR   KEGG; ag:AAK73513; -.
DR   EvolutionaryTrace; Q93NW7; -.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR   GO; GO:0033068; P:macrolide biosynthetic process; IEA:UniProt.
DR   CDD; cd08952; KR_1_SDR_x; 2.
DR   CDD; cd00833; PKS; 2.
DR   Gene3D; 3.30.70.3290; -; 2.
DR   Gene3D; 3.40.47.10; -; 2.
DR   Gene3D; 6.10.140.1830; -; 1.
DR   Gene3D; 1.10.1200.10; ACP-like; 2.
DR   Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 2.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR   InterPro; IPR001227; Ac_transferase_dom_sf.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR014043; Acyl_transferase.
DR   InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR   InterPro; IPR018201; Ketoacyl_synth_AS.
DR   InterPro; IPR014031; Ketoacyl_synth_C.
DR   InterPro; IPR014030; Ketoacyl_synth_N.
DR   InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR032821; PKS_assoc.
DR   InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR   InterPro; IPR041618; PKS_DE.
DR   InterPro; IPR013968; PKS_KR.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR015083; Polyketide_synth_docking.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   InterPro; IPR016039; Thiolase-like.
DR   PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR   PANTHER; PTHR43775:SF51; PHENOLPHTHIOCEROL_PHTHIOCEROL POLYKETIDE SYNTHASE SUBUNIT E; 1.
DR   Pfam; PF00698; Acyl_transf_1; 2.
DR   Pfam; PF08990; Docking; 1.
DR   Pfam; PF16197; KAsynt_C_assoc; 2.
DR   Pfam; PF00109; ketoacyl-synt; 2.
DR   Pfam; PF02801; Ketoacyl-synt_C; 2.
DR   Pfam; PF08659; KR; 2.
DR   Pfam; PF18369; PKS_DE; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SMART; SM00827; PKS_AT; 2.
DR   SMART; SM00822; PKS_KR; 2.
DR   SMART; SM00825; PKS_KS; 2.
DR   SMART; SM00823; PKS_PP; 2.
DR   SMART; SM01294; PKS_PP_betabranch; 2.
DR   SUPFAM; SSF47336; ACP-like; 2.
DR   SUPFAM; SSF52151; FabD/lysophospholipase-like; 2.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 4.
DR   SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 2.
DR   SUPFAM; SSF53901; Thiolase-like; 2.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00606; KS3_1; 2.
DR   PROSITE; PS52004; KS3_2; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE   1: Evidence at protein level;
KW   3D-structure {ECO:0007829|PDB:3MJC, ECO:0007829|PDB:3MJE};
KW   Acyltransferase {ECO:0000256|ARBA:ARBA00023315};
KW   Antibiotic biosynthesis {ECO:0000256|ARBA:ARBA00023194};
KW   Nucleotide-binding {ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS};
KW   Phosphopantetheine {ECO:0000256|ARBA:ARBA00022450};
KW   Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679}.
FT   DOMAIN          38..459
FT                   /note="Ketosynthase family 3 (KS3)"
FT                   /evidence="ECO:0000259|PROSITE:PS52004"
FT   DOMAIN          1479..1554
FT                   /note="Carrier"
FT                   /evidence="ECO:0000259|PROSITE:PS50075"
FT   DOMAIN          1575..2002
FT                   /note="Ketosynthase family 3 (KS3)"
FT                   /evidence="ECO:0000259|PROSITE:PS52004"
FT   DOMAIN          3031..3106
FT                   /note="Carrier"
FT                   /evidence="ECO:0000259|PROSITE:PS50075"
FT   BINDING         2757
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2757
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2758
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2758
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2779
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2779
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2780
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2780
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2807
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2807
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2808
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2808
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2833
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2833
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2834
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2834
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJS, ECO:0007829|PDB:3MJT"
FT   BINDING         2835
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2835
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2858
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2858
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2895
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJT"
FT   BINDING         2924
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2924
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
FT   BINDING         2929
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0007829|PDB:5XWW"
FT   BINDING         2929
FT                   /ligand="NADPH"
FT                   /ligand_id="ChEBI:CHEBI:57783"
FT                   /evidence="ECO:0007829|PDB:3MJE, ECO:0007829|PDB:3MJS"
SQ   SEQUENCE   3190 AA;  334066 MW;  EC005DABF792D89B CRC64;
     MPEPQQNQQE KVVDYLRRVT NDLRRARRRI GELESRDNEP VAIVGMSCRL PGGVSSPESL
     WELVESGGDA ISGFPADRGW DIEALTGKGE GSSSTHEGGF LYEATDFDAG FFGISPREAT
     AMDPQQRLLL EVSWEALERA GIAPTSLRSS ATGVFVGSYH WGAPSADTAT ELHGHALTGT
     AASVLSGRLS YVYGLEGPAV TVDTACSSSL VALHMAAQSL RNGESSLALV GGVTILAEPS
     VFVEFSAQGG LAQDGRCKAF SDSADGTGWS EGAAVLVVER LSDARRAGHR VLAVVRGSAV
     NQDGASNGLT APNGPSQQRV IRQALANAGL RPGDVDAVEA HGTGTPLGDP IEAQALIATY
     GSDRDPQQPL LLGSVKSNIG HTQSAAGVAG LVKMVMAMHN GTLPRTLHLT EPSTHVDWSL
     GAVRLLTEET AWPETGRVRR AAVSSFGISG TNAHAVLEQA PVPAEDAEDA GTEDAPQQPA
     TVPGALPWLL SAHSGQALCD QAAALVTRLD ADPEPRPQDI GQGLLTSRAL LERRAVVVGT
     GRDELLTGSR ALAEGQSWNG LAEGTADVDG RTVFVFPGQG SQWVGMGARL LDESPVFAER
     IAECAAALAE FTDWDLLDVL RGAEGAPTLE RVDVVQPASF AVMVSLAAVW RAQGVEPDAV
     VGHSQGEIAA AVVSGALSLR DGARVVALRS QAIGRTLAGR GGMMSVALPV ADVEARLEAF
     GGRVSVAAEN GPRSCVVSGE PGALDELSEL LTAEGVRVRR VPVDYASHSH HVEDLHDEIL
     QLLAEVAPKA SEVPLFSTVT GDWLDTTVMD AGYWFRSLRG RVLFADAIRG LLDTEHRAFI
     EVSSHPVLAM SVQDMIDDAG VVGVASGTLR RDNGGLDRFL LSAAQVFVRG VQVDWAPLFE
     GTGATRVDLP TYAFQHERYW NDRAVVDRSA SAPMDAEFWA AVEQADVSAL TEALGTDEES
     VAAILPGLAS WRRTRGERST VDSWRYRVVW EPLAQIPRAT LDGTWLLVSA GGVDDDVAEV
     LEAGGAEVRR LVLDETCTDP AVLREHLTDT DGLTGIVSVL ADAEEGCVRH PGLTLGLALS
     VSLAQALGEA DVTAPLWFLT CGAFSTGPSD TVTRPLQSQI AGLGWTVAVE HPHRWGGGVD
     LPEALDARAA QRLVAALAGA LGDDDQLAVR PAGVLARRIV RASGDTRRKA RSWKPRGTTL
     VTGGSGTLAP GLARHLAAQG AEHLVLLSRR GADAPGAAEL AAELQAAGTE VRFAACDITD
     PDAVAALLAD LKAEGRTVRT VVHTAAVIEL AALADTTVDA FADVVHAKVT GARILDELLD
     DEELDDFVLY SSTAGMWGSG VHAAYVAGNA YLSALAEQRR ARGARATSIH WGKWPDDLER
     ELADPHQIRR SGLEYLDPEL AMTALTRVME DDETVIGLMD IDWGTYHDVF TAGRPSHLFD
     RIPEVARLLA DRAAPAATAV ATSGLAARLQ GVSAAEQDRI VLSVVREETA AVLGHASAET
     VPERRAFRDI GFDSVTAVDL RNRLVAATGL TLPSTMVFDH PNAVALATFL KATALGTTGT
     AGDRPTAAVT AGADDDLIVI VGMSCRFPGG ANTPEELLRL ALDGADVISE FPADRGWDAH
     GLYDPDPDRQ GRTYSVHGGF LHEAAGFDAG FFGISPREAL AMDPQQRLLL ETSWEVLERA
     GIDPESLHST ATGAFFGASY QDYSSSVQNG TEGAEVHMMT GTAASVLSGR ISYLLGLEGP
     AVTVDTACSS SLVAMHLACQ SLRSGESSLA LAGGAAVMAT PHAFIGFSRQ RALAENGRCK
     PFAEGADGMT LAEGVGVVLL EKLSDARRNG HRVLAVVRGS ALNQDGASNG LTAPNGLSQQ
     RVIRQALANA GLGTADIDVV EAHGTGTKLG DPIEAGALLA TYGQGRDGGQ PLLLGSVKSN
     IGHTQAAAGV AGVIKMVMAM HAGELPGTLH IDEPSSHVDW TSGAVTLLRE RTEWPAVGDR
     PRRAGISSFG ISGTNAHLLL EQAPPAEEPA EEPAGDIEGA PLVPWLLSAR SAQALREQAS
     RLLTATTGTD VTVEPARVGH ALATTRTAFD HRAVVLGSRP EDFTRGLEAV VSSASAPGVV
     TGTAGPDSTG PVFVYPGQGS QWWGMGRELL AGSEVFRTAV DDCAAALAPY TDWSLHEVLA
     GEGDPELLER VDVVQPALFS MMVALTALWR SHGVEPAAVV GHSQGEIAAA HVAGALSLED
     AALVVALRSQ ALPQLSGLGG MMSVSAPAAR VTELLQPWGE ALSIAAVNGP SSVIVSGDAD
     ALDELLETCR EQNVRARKVS VDYASHGRHV EAVRDELARV LAPVSPRTPE VPFYSTVTGA
     RLDEAAFDGT YWYTNLRQTV LMEDATRALI ASGHRVFVEI SPHPVLAAPI QETQESVQEE
     LTETGAVLGT LRRDDGDRRR FLTSLAEAHT HGIAVDWTTA FDRPAYAAVD LPTYPFQRQD
     FWPEPKTAAP AGTADASDAA FWELVQNQDL DALAGELGIP ADDGAARLGD VLPALSAWRT
     RSLTRSRADA LRYHIEWNRV AEPGTARPAG RLLAVISPDH AGAPWVTAVL DALGPDTVRF
     EAKGTDRAAW AAQLAQLRED EGEFHAVVSL LAAAEALHTD HGSVPLGLAQ TLLLAQALGD
     AGLTAPLWCL TRGGVAAGRG DVLSSPVQGA LWGLGRVIGL EHPDRWGGLI DLPETVDTRA
     AARLTGLLAD AGGEDQLAIR GSGVLARRLA HAAPAVPGSG KRPPVHGSVL VTGGTGGIGG
     RVARRLAEQG AAHLVLTSRR GADAPGAAEL RAELEQLGVR VTIAACDAAD REALAALLAE
     LPEDAPLTAV FHSAGVAHDD APVADLTLGQ LDALMRAKLT AARHLHELTA DLDLDAFVLF
     SSGAAVWGSG GQPGYAAANA YLDALAEHRR SLGLTASSVA WGTWGEVGMA TDPEVHDRLV
     RQGVLAMEPE HALGALDQML ENDDTAAAIT LMDWEMFAPA FTANRPSALL STVPEAVSAL
     SDEGPADGGA DAAVPPLRAR LDGLPTAERA RALVEAVRAE ASATLGHDSP DAVPASRAFR
     DVGFDSVTAV ELRNRLRAAL GLPLPAALVF DYPTPTALAQ HIGSLLYGTA PDEADTGRAD
     DPDARIREAL ATVPIGRLRK AGLLDMVLKL AESDDTEDSA TATDDAADAL DLDDMDAEAL
     LRLAAENSAN
//