ID CRTM_STAA8 Reviewed; 287 AA. AC Q2FV59; DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2006, sequence version 1. DT 05-OCT-2010, entry version 34. DE RecName: Full=Dehydrosqualene synthase; DE EC=2.5.1.-; DE AltName: Full=4,4'-diapophytoene synthase; DE Short=DAP synthase; DE AltName: Full=Diapophytoene synthase; GN Name=crtM; OrderedLocusNames=SAOUHSC_02879; OS Staphylococcus aureus (strain NCTC 8325). OC Bacteria; Firmicutes; Bacillales; Staphylococcus. OX NCBI_TaxID=93061; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., RA Iandolo J.J.; RT "The Staphylococcus aureus NCTC8325 genome."; RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF PHE-26. RX PubMed=12426357; DOI=10.1128/JB.184.23.6690-6699.2002; RA Umeno D., Tobias A.V., Arnold F.H.; RT "Evolution of the C(30) carotenoid synthase crtM for function in a RT C(40) pathway."; RL J. Bacteriol. 184:6690-6699(2002). RN [3] RP SUBSTRATE SPECIFICITY. RX PubMed=12788765; DOI=10.1128/AEM.69.6.3573-3579.2003; RA Umeno D., Arnold F.H.; RT "A C(35) carotenoid biosynthetic pathway."; RL Appl. Environ. Microbiol. 69:3573-3579(2003). RN [4] RP MUTAGENESIS OF TRP-38 AND GLU-180. RX PubMed=12907743; DOI=10.1093/nar/gng091; RA Umeno D., Hiraga K., Arnold F.H.; RT "Method to protect a targeted amino acid residue during random RT mutagenesis."; RL Nucleic Acids Res. 31:E91-E91(2003). RN [5] RP MUTAGENESIS OF PHE-26; TRP-38 AND GLU-180. RX PubMed=14973014; DOI=10.1128/JB.186.5.1531-1536.2004; RA Umeno D., Arnold F.H.; RT "Evolution of a pathway to novel long-chain carotenoids."; RL J. Bacteriol. 186:1531-1536(2004). RN [6] RP FUNCTION, AND KINETIC PARAMETERS. RX PubMed=16269684; DOI=10.1128/AEM.71.11.6578-6583.2005; RA Ku B., Jeong J.-C., Mijts B.N., Schmidt-Dannert C., Dordick J.S.; RT "Preparation, characterization, and optimization of an in vitro C(30) RT carotenoid pathway."; RL Appl. Environ. Microbiol. 71:6578-6583(2005). CC -!- FUNCTION: Catalyzes the head-to-head condensation of two molecules CC of farnesyl diphosphate (FPP) into the colorless C(30) carotenoid CC dehydrosqualene (4,4'-diapophytoene). This is the initial step in CC the biosynthesis of staphyloxanthin, an orange carotenoid present CC in most staphylococci strains. CC -!- CATALYTIC ACTIVITY: 2 farnesyl diphosphate = diphosphate + CC presqualene diphosphate. CC -!- CATALYTIC ACTIVITY: Presqualene diphosphate = diphosphate + CC dehydrosqualene. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.2 uM for farnesyl diphosphate; CC Vmax=176 uM/h/mg enzyme; CC -!- PATHWAY: Carotenoid biosynthesis; staphyloxanthin biosynthesis; CC staphyloxanthin from farnesyl diphosphate: step 1/5. CC -!- MISCELLANEOUS: CrtM is not functional in a C(40) pathway, however CC independent mutations on Phe-26, Trp-38 or Glu-180 are sufficient CC to permit the synthesis of C(40) carotenoids, such as lycopene and CC 3,4,3',4'-tetrahydrolycopene, although there is a decrease in the CC synthesis of C(30) compounds. The combination of mutations at Phe- CC 26 and Trp-38 appears to be harmful for the general performance of CC the enzyme. CC -!- MISCELLANEOUS: Upon coexpression with Erwinia CC geranylgeranyldiphosphate (GGDP) synthase, crtM produces novel CC carotenoids with the asymmetrical C(35) backbone, such as 4- CC apophytoene, and the production of the natural product 4,4'- CC diapophytoene drops dramatically. CC -!- SIMILARITY: Belongs to the phytoene/squalene synthase family. CrtM CC subfamily. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000253; ABD31876.1; -; Genomic_DNA. DR RefSeq; YP_501333.1; -. DR ProteinModelPortal; Q2FV59; -. DR SMR; Q2FV59; 1-284. DR STRING; Q2FV59; -. DR EnsemblBacteria; EBSTAT00000028867; EBSTAP00000027818; EBSTAG00000028865. DR GeneID; 3921549; -. DR GenomeReviews; CP000253_GR; SAOUHSC_02879. DR KEGG; sao:SAOUHSC_02879; -. DR eggNOG; COG1562; -. DR HOGENOM; HBG693191; -. DR OMA; RFGYSEA; -. DR ProtClustDB; CLSK886072; -. DR BioCyc; SAUR93061:SAOUHSC_02879-MONOMER; -. DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW. DR GO; GO:0016117; P:carotenoid biosynthetic process; IEA:UniProtKB-KW. DR InterPro; IPR002060; Squ/phyt_synthse. DR InterPro; IPR019845; Squalene/phytoene_synthase_CS. DR InterPro; IPR008949; Terpenoid_synth. DR Gene3D; G3DSA:1.10.600.10; Terpenoid_synth; 1. DR Pfam; PF00494; SQS_PSY; 1. DR SUPFAM; SSF48576; Terpenoid_synth; 1. DR PROSITE; PS01044; SQUALEN_PHYTOEN_SYN_1; 1. DR PROSITE; PS01045; SQUALEN_PHYTOEN_SYN_2; FALSE_NEG. PE 1: Evidence at protein level; KW Carotenoid biosynthesis; Complete proteome; Transferase. FT CHAIN 1 287 Dehydrosqualene synthase. FT /FTId=PRO_0000282616. FT REGION 18 22 Farnesyl diphosphate 1 binding (By FT similarity). FT REGION 45 48 Farnesyl diphosphate 2 binding (By FT similarity). FT BINDING 41 41 Farnesyl diphosphate 1 (By similarity). FT BINDING 168 168 Farnesyl diphosphate 2 (By similarity). FT BINDING 171 171 Farnesyl diphosphate 1 (By similarity). FT BINDING 172 172 Farnesyl diphosphate 2 (By similarity). FT BINDING 248 248 Farnesyl diphosphate 1 (By similarity). FT MUTAGEN 26 26 F->A,G,L,S: Decrease in C(30) carotene FT synthase activity. C(40) carotene FT synthase activity acquired. FT MUTAGEN 26 26 F->A: Decrease in C(30) and C(40) FT carotene synthase activities; when FT associated with A-38 or G-38. FT MUTAGEN 26 26 F->G: Decrease in C(30) and C(40) FT carotene synthase activities; when FT associated with A-38 or G-38. FT MUTAGEN 38 38 W->A: Decrease in C(30) and C(40) FT carotene synthase activities; when FT associated with A-26 or G-26. FT MUTAGEN 38 38 W->C: Decrease in C(30) carotene synthase FT activity. C(40) carotene synthase FT activity acquired. FT MUTAGEN 38 38 W->G: Decrease in C(30) and C(40) FT carotene synthase activities; when FT associated with A-26 or G-26. FT MUTAGEN 180 180 E->G: Slight increase in C(30) carotene FT synthase activity. C(40) carotene FT synthase activity acquired. SQ SEQUENCE 287 AA; 34231 MW; 2407009413D42E63 CRC64; MTMMDMNFKY CHKIMKKHSK SFSYAFDLLP EDQRKAVWAI YAVCRKIDDS IDVYGDIQFL NQIKEDIQSI EKYPYEHHHF QSDRRIMMAL QHVAQHKNIA FQSFYNLIDT VYKDQHFTMF ETDAELFGYC YGVAGTVGEV LTPILSDHET HQTYDVARRL GESLQLINIL RDVGEDFDNE RIYFSKQRLK QYEVDIAEVY QNGVNNHYID LWEYYAAIAE KDFQDVMDQI KVFSIEAQPI IELAARIYIE ILDEVRQANY TLHERVFVDK RKKAKLFHEI NSKYHRI //