ID   LCPS_NEUCR              Reviewed;         602 AA.
AC   P37295; Q7RVN3;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1994, sequence version 1.
DT   10-JUN-2026, entry version 138.
DE   RecName: Full=Bifunctional lycopene cyclase/phytoene synthase {ECO:0000303|PubMed:11862485};
DE   AltName: Full=Protein albino-2;
DE   Includes:
DE     RecName: Full=Lycopene beta-cyclase {ECO:0000303|PubMed:11862485};
DE              EC=5.5.1.19 {ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
DE     AltName: Full=Carotene cyclase {ECO:0000303|PubMed:11862485};
DE     AltName: Full=Lycopene cyclase {ECO:0000303|PubMed:11862485};
DE   Includes:
DE     RecName: Full=Phytoene synthase {ECO:0000303|PubMed:8163509};
DE              EC=2.5.1.32 {ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
GN   Name=al-2 {ECO:0000303|PubMed:8163509}; ORFNames=B22I21.230, NCU00585;
OS   Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS   FGSC 987).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX   NCBI_TaxID=367110;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=8163509; DOI=10.1016/s0021-9258(17)32680-7;
RA   Schmidhauser T.J., Lauter F.-R., Schumacher M., Zhou W., Russo V.E.A.,
RA   Yanofsky C.;
RT   "Characterization of al-2, the phytoene synthase gene of Neurospora crassa.
RT   Cloning, sequence analysis, and photoregulation.";
RL   J. Biol. Chem. 269:12060-12066(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12655011; DOI=10.1093/nar/gkg293;
RA   Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D.,
RA   Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U.;
RT   "What's in the genome of a filamentous fungus? Analysis of the Neurospora
RT   genome sequence.";
RL   Nucleic Acids Res. 31:1944-1954(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA   Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA   Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA   Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA   Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA   Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA   Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA   Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TRP-189 AND LYS-208.
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=11862485; DOI=10.1007/s00438-001-0626-5;
RA   Arrach N., Schmidhauser T.J., Avalos J.;
RT   "Mutants of the carotene cyclase domain of al-2 from Neurospora crassa.";
RL   Mol. Genet. Genomics 266:914-921(2002).
RN   [5]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=16928467; DOI=10.1016/j.bbalip.2006.06.002;
RA   Sandmann G., Zhu C., Krubasik P., Fraser P.D.;
RT   "The biotechnological potential of the al-2 gene from Neurospora crassa for
RT   the production of monocyclic keto hydroxy carotenoids.";
RL   Biochim. Biophys. Acta 1761:1085-1092(2006).
CC   -!- FUNCTION: Bifunctional enzyme that catalyzes the reactions from
CC       geranylgeranyl diphosphate to phytoene (phytoene synthase) and from
CC       lycopene to beta-carotene via the intermediate gamma-carotene and from
CC       3,4-didehydrolycopene to torulene (lycopene cyclase). Torulene is
CC       further processed to the acidic carotenoid neurosporaxanthin. The
CC       cyclase preferentially catalyzes single cyclizations at only one end of
CC       the substrate to produce monocyclic carotenoids (PubMed:11862485,
CC       PubMed:16928467). Neurosporaxanthin is synthesized from geranyl-geranyl
CC       pyrophosphate (GGPP) through several enzymatic activities. Phytoene
CC       synthase activity performed by the bifunctional enzyme al-2 first
CC       produces phytoene from geranyl-geranyl pyrophosphate (GGPP). The
CC       phytoene dehydrogenase al-1 then introduces 5 desaturations to lead to
CC       3,4-didehydrolycopene via the intermediates phytofluene, zeta-carotene,
CC       neurosporene and lycopene. Al-2 cyclase activity then converts 3,4-
CC       didehydrolycopene into torulene. Al-2 can also convet lycopene into
CC       gamma-carotene which in turn is converted to beta-carotene by an
CC       additional al-2 cyclization reaction. Torulene is the substrate of the
CC       dioxidase cao-2 that breaks the molecule, removing five carbon atoms to
CC       yield beta-apo-4'-carotenal, whereas the aldehyde dehydrogenase ylo-1
CC       mediates the last step by converting beta-apo-4'-carotenal into
CC       neurosporaxanthin (Probable). {ECO:0000269|PubMed:11862485,
CC       ECO:0000269|PubMed:16928467, ECO:0000305|PubMed:11862485}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=all-trans-lycopene = gamma-carotene; Xref=Rhea:RHEA:32219,
CC         ChEBI:CHEBI:15948, ChEBI:CHEBI:27740; EC=5.5.1.19;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=gamma-carotene = all-trans-beta-carotene;
CC         Xref=Rhea:RHEA:32239, ChEBI:CHEBI:17579, ChEBI:CHEBI:27740;
CC         EC=5.5.1.19; Evidence={ECO:0000269|PubMed:11862485,
CC         ECO:0000269|PubMed:16928467};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 (2E,6E,10E)-geranylgeranyl diphosphate = 15-cis-phytoene + 2
CC         diphosphate; Xref=Rhea:RHEA:34475, ChEBI:CHEBI:27787,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58756; EC=2.5.1.32;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34476;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 (2E,6E,10E)-geranylgeranyl diphosphate = (1R,2R,3R)-
CC         prephytoene diphosphate + diphosphate; Xref=Rhea:RHEA:22296,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58011, ChEBI:CHEBI:58756;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22297;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(1R,2R,3R)-prephytoene diphosphate = 15-cis-phytoene +
CC         diphosphate; Xref=Rhea:RHEA:34479, ChEBI:CHEBI:27787,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58011;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34480;
CC         Evidence={ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467};
CC   -!- PATHWAY: Carotenoid biosynthesis; beta-carotene biosynthesis.
CC       {ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467}.
CC   -!- PATHWAY: Carotenoid biosynthesis; phytoene biosynthesis; all-trans-
CC       phytoene from geranylgeranyl diphosphate: step 1/1.
CC       {ECO:0000269|PubMed:11862485, ECO:0000269|PubMed:16928467}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: By blue light.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the lycopene beta-
CC       cyclase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the phytoene/squalene
CC       synthase family. {ECO:0000305}.
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DR   EMBL; L27652; AAA19428.1; -; Genomic_DNA.
DR   EMBL; BX842641; CAE76609.1; -; Genomic_DNA.
DR   EMBL; CM002236; EAA36489.3; -; Genomic_DNA.
DR   PIR; A53583; A53583.
DR   RefSeq; XP_965725.3; XM_960632.3.
DR   AlphaFoldDB; P37295; -.
DR   SMR; P37295; -.
DR   STRING; 367110.P37295; -.
DR   PaxDb; 367110-P37295; -.
DR   EnsemblFungi; EAA36489; EAA36489; NCU00585.
DR   GeneID; 3881954; -.
DR   KEGG; ncr:NCU00585; -.
DR   VEuPathDB; FungiDB:NCU00585; -.
DR   HOGENOM; CLU_012965_0_0_1; -.
DR   InParanoid; P37295; -.
DR   OrthoDB; 6600518at2759; -.
DR   BioCyc; MetaCyc:MONOMER-16129; -.
DR   UniPathway; UPA00799; UER00773.
DR   UniPathway; UPA00802; -.
DR   Proteomes; UP000001805; Chromosome 1, Linkage Group I.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0046905; F:15-cis-phytoene synthase activity; IDA:UniProtKB.
DR   GO; GO:0004311; F:geranylgeranyl diphosphate synthase activity; IEA:InterPro.
DR   GO; GO:0016872; F:intramolecular lyase activity; IEA:InterPro.
DR   GO; GO:0045436; F:lycopene beta cyclase activity; IDA:UniProtKB.
DR   GO; GO:0051996; F:squalene synthase [NAD(P)H] activity; IEA:InterPro.
DR   GO; GO:0016120; P:carotene biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0016117; P:carotenoid biosynthetic process; IDA:UniProt.
DR   CDD; cd00683; Trans_IPPS_HH; 1.
DR   FunFam; 1.10.600.10:FF:000018; Probable geranylgeranyl-diphosphate geranylgeranyltransferase (AL-2); 1.
DR   Gene3D; 1.10.600.10; Farnesyl Diphosphate Synthase; 1.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR017825; Lycopene_cyclase_dom.
DR   InterPro; IPR002060; Squ/phyt_synthse.
DR   InterPro; IPR019845; Squalene/phytoene_synthase_CS.
DR   InterPro; IPR044843; Trans_IPPS_bact-type.
DR   InterPro; IPR033904; Trans_IPPS_HH.
DR   NCBIfam; TIGR03462; CarR_dom_SF; 2.
DR   PANTHER; PTHR31480; BIFUNCTIONAL LYCOPENE CYCLASE/PHYTOENE SYNTHASE; 1.
DR   Pfam; PF18916; Lycopene_cyc; 1.
DR   Pfam; PF00494; SQS_PSY; 1.
DR   SFLD; SFLDS00005; Isoprenoid_Synthase_Type_I; 1.
DR   SFLD; SFLDG01212; Phytoene_synthase_like; 1.
DR   SFLD; SFLDG01018; Squalene/Phytoene_Synthase_Lik; 1.
DR   SUPFAM; SSF48576; Terpenoid synthases; 1.
DR   PROSITE; PS01044; SQUALEN_PHYTOEN_SYN_1; 1.
DR   PROSITE; PS01045; SQUALEN_PHYTOEN_SYN_2; 1.
PE   1: Evidence at protein level;
KW   Carotenoid biosynthesis; Isomerase; Membrane; Multifunctional enzyme;
KW   Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..602
FT                   /note="Bifunctional lycopene cyclase/phytoene synthase"
FT                   /id="PRO_0000067440"
FT   TRANSMEM        6..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        30..50
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        146..166
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        230..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..241
FT                   /note="Lycopene beta-cyclase"
FT                   /evidence="ECO:0000305|PubMed:8163509"
FT   REGION          248..602
FT                   /note="Phytoene synthase"
FT                   /evidence="ECO:0000305|PubMed:8163509"
FT   MUTAGEN         189
FT                   /note="W->R: In JA26; Abolishes lycopene cyclase activity
FT                   and accumulates a polar precursor carotenoid of
FT                   neurosporaxanthin."
FT                   /evidence="ECO:0000269|PubMed:11862485"
FT   MUTAGEN         208
FT                   /note="K->E: In JA28; Abolishes lycopene cyclase activity
FT                   and accumulates a polar precursor carotenoid of
FT                   neurosporaxanthin."
FT                   /evidence="ECO:0000269|PubMed:11862485"
SQ   SEQUENCE   602 AA;  68928 MW;  DDFFBD725007E5C2 CRC64;
     MYDYAFVHLK FTVPAAVLLT AIAYPILNRI HLIQTGFLVV VAFTAALPWD AYLIKHKVWS
     YPPEAIVGPR LLGIPFEELF FFVIQTYITA LVYILFNKPV LHALHLNNQQ NPPAWMRVVK
     VTGQVVLVAL SVWGWNAAQV HQETSYLGLI LVWACPFLLA IWTLAGRFIL SLPWYATVLP
     MFLPTFYLWA VDEFALHRGT WSIGSGTKLD FCLFGKLDIE EATFFLVTNM LIVGGMAAFD
     QYLAVIYAFP TLFPKVNRYP TTHMLLQSRL INTSRYDLER IEGLREAVER LRLKSRSFYL
     ANSLFSGRLR IDLILLYSFC RLADDLVDDA KSRREVLSWT AKLNHFLDLH YKDADATEDP
     KKKAERIDAY IKTAFPPCAY QALHLLPTHI LPPKPLYDLI KGFEMDSQFT FHGTSDSTDL
     QYPIADDKDL ENYAIYVAGT VGELCIALII YHCLPDMSDT QKRELETAAC RMGIALQYVN
     IARDIVVDAR IGRVYLPTTW LKKEGLTHKM VLENPEGPEV IERMRRRLLE NAFELYGGAR
     PEMQRIPSEA RGPMIGAVEN YMAIGRVLRE RKEGTVFVRM EGRATVPKRR RLSTLLRALY
     EQ
//