DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Preliminary Amendment filed on September 11, 2023, has been received and entered.
Restriction Requirement
3. Applicant’s election of Group I without traverse, on June 11, 2026, is acknowledged.
Claim Disposition
4. Claims 1-96 are canceled. Claims 97-116 have been added. Claims 97-116 are pending. Claim 97 is under examination. Claims 98-116 are withdrawn from further consideration pursuant to 37 CFR1.12(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim. Claim 97 is only being examined to the extent that it pertains to the elected subject matter.
Information Disclosure Statement
5. The Information Disclosure Statement filed on September 11, 2023, has been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action. Note that a reference has been lined through based on an improper citation of the date.
Drawing
6. The Drawings filed on September 11, 2023, are accepted by the examiner.
Abstract Objection
7. The abstract is objected to for the following informalities:
a) Applicant should spell out ‘for example’.
b) Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Specification Objection
8. The specification is objected to for the following informalities:
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: "A fungal luciferin biosynthesis protein and methods of using the same".
The specification is also objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. See page 92, for example. It is suggested that http:// is deleted.
The specification is objected to because the organism names are not italicized, see Arabidopsis thaliana on page 125.
The specification is objected to for the typographical error that appears on page 132 of [[SEQ ID NO 141]], which should be “SEQ ID NO: 141”. See also throughout the specification).
Appropriate correction is required.
Claim objection
9. Claim 97 is objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to recite “……selected from the [[following]] group consisting of : SEQ ID NOs: [[NOs group:]] 2, 4, 6,8…….and 28, or contains consensus sequences [[with the]] selected from the group consisting of : SEQ ID NOs: 29, 30, 31, 32 and 33, [[SEQ ID NOs 29-33]] separated by …..” (see the rest of the claim with similar language ( items b and c) that also needs to be corrected).
For clarity it is suggested that claim 97 is amended to link items a, b, c with a transitional phrase (for example, a, b and c).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
10. Claim 97 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention is directed to “a fungal luciferin biosynthesis protein selected from (a) hispidin hydroxylases……(b) hispidin synthases….. and (c) caffeylpyruvate hydroxylases…..”. The claimed invention is not adequately described because it encompasses a large variable genus of structures with the recitation of “60% identity”; 45% identity and at least 60% identity to the claimed sequences which has a vast amount of variability.
The claimed invention is overly broad and not commensurate in scope with the disclosure in the specification because the invention includes analogs, derivatives, fragments etc. with the recitation of the aforementioned percentages and no alignment is made with a specific structure that is 45% with retention of activity. The claimed invention does not inform the ordinary skilled worker of the specific product, as no correlation is made between structure and function. The claimed invention encompasses a large variable genus of structures for the protein, that is not adequately described. The art recognizes that a single change in the protein structure can be detrimental for functioning, which would produce a different structure and which makes the instant claim language overly broad. The structural difference could render the protein as non-functional. The claimed invention is not adequately described because the claims far exceed the scope of the disclosure in the specification and the art.
Thus the claimed invention is not adequately described because there is no demonstration of applicant being in possession of the vast genus encompassed in the claims.
The specification fails to provide a representative number of species for the claimed genus to show that applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described, are representative of the entire genus.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by
functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
11. Claim(s) 97 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Angew et al., ("The chemical basis of fungal bioluminescence", Chem. Int. Ed. 54:8124-8128 (2015), of record in the application).
The claimed invention is directed to a fungal luciferin biosynthesis protein with a structure selected from groups (a)-(c), which encompasses percentages of identity to sequences and alternative language for a consensus sequence. The claims list groups/Markush language and do not recite any transitional phrase thus for purposes of art are interpreted as not being linked/related.
Angew et al. teach a bioluminescent fungi. The reference discloses the luciferin/luciferase systems. Angew et al. teach hispidin, hispidin-3-hydroxylase which produces 3-hydroxyhispidin that acts as the fungal luciferin (see abstract and page 1 of the reference). The structure taught by the reference anticipates the percentage language and the full-length structure of SEQ ID NO: 2 (see the below alignment). Angew et al. teach caffeic acid and discloses compounds found in the claim (see pages 2- 3 of the reference). Therefore, the limitations of the claims are met by the reference.
12. Claim(s) 97 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kotlobay et al., ("Genetically encodable bioluminescent system from fungi", PNAS, 115(50) 12728-12732 (received February 28, 2018) of record in the application).
The claimed invention is directed to a fungal luciferin biosynthesis protein with a structure selected from groups (a)-(c).
Kotlobay et al. teach a bioluminescent fungi. The reference discloses luciferin from caffeic acid (see page 12728). Kotlobay et al. teach hispidin synthase, hispidin hydroxylase and caffeylpyruvate hydroxylase (see FIG. 1 for example). The structures in the claim is anticipated (see the below alignments as evidence, the consensus sequences are written in the alternative.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
13. Claim 97 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claim(s) 97 is/are directed to, “a fungal luciferin biosynthesis protein with reads on 100% sequence identity to the recited sequences such as SEQ ID NO: 2, SEQ ID NO: 35 and SEQ ID NO: 65. The claimed invention is not described as being isolated or purified either to demonstrate the hand of man. Furthermore, the fungal luciferin biosynthesis protein reads on a product found in nature also because it is not markedly different from the judicial exception under Myriad. With the recitation of ‘at least 60%, 45% and 60% pertaining respectively to the aforementioned sequences, this does not exclude 100%, the native structure. The dependent claims recite more percentages that also read on the native structure or a truncated contiguous run of sequences found in nature. The claim(s) does/do not include additional elements that are sufficient to amount to ‘significantly more’ than the judicial exception because the claimed invention encompasses products that have characteristics that are not markedly different from the product’s naturally occurring counterpart in its natural state.
The rationale for this determination is provided below: The claimed protein appears to be naturally occurring, it is from a fungus and not established as isolated in the claims and does not appear to be markedly different than the judicial exception. The fact pattern in the application is that the claims are directed to a product that initially appears non-naturally occurring, however is a natural product. The scope of the claims is not limited a non-naturally occurring product.
The judicial exception is recited with general instructions to apply or use the judicial exception (which does not alter the structure of the protein). An analysis of the claimed invention as a whole indicates that the claims are directed to a product that on its face does not satisfy the hand of man (see American Wood v. Fiber Disintegrating Co., 90 U. S. 566 (1974); American Fruit Growers v. Brogdex Co., 283 U. S. 1 (1931); Funk Brothers Seed Co. v. Kalo Inoculant, 33 U. S. 127 (1948); and Diamond v. Chakrabarty, 206 USPQ 193 (1980), and it is also concluded that the product is not markedly different in structure from the naturally occurring counterpart products. The claimed invention as a whole is not informative because while the claims are limited to a particular structure, the claimed product is claimed with a very high level of generality.
A truncation of a structure does not render it non-natural and the percentages reads on a 100% in the claims. There is no additional element reported in the claimed invention the makes clear that the instantly claimed protein is markedly different (see Funk Brothers Seed Co., V. Kalo Inoculant Co., 333 U.S. 127, 1948 and Association for Molecular Pathology v. Myriad Genetics, Inc. 569 U.S., 133 S.Ct.2107, 2116, 106 USPQ 2d. 1972).
ALIGNMENTS
ALIGNMENT: SEQ ID NO:2
RESULT 1
H3H_NEONM
ID H3H_NEONM Reviewed; 422 AA.
AC A0A3G9K5C8;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Hispidin-3-hydroxylase {ECO:0000303|PubMed:30478037};
DE Short=H3H {ECO:0000303|PubMed:30478037};
DE EC=1.-.-.- {ECO:0000269|PubMed:26094784};
DE AltName: Full=FAD-dependent monooxygenase h3h {ECO:0000303|PubMed:30478037};
DE AltName: Full=Fungal bioluminescence cycle protein h3h {ECO:0000303|PubMed:30478037};
GN Name=h3h {ECO:0000303|PubMed:30478037};
OS Neonothopanus nambi (Agaricus nambi).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Omphalotaceae; Neonothopanus.
OX NCBI_TaxID=71958;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION, FUNCTION, PATHWAY, AND
RP BIOTECHNOLOGY.
RX PubMed=30478037; DOI=10.1073/pnas.1803615115;
RA Kotlobay A.A., Sarkisyan K.S., Mokrushina Y.A., Marcet-Houben M.,
RA Serebrovskaya E.O., Markina N.M., Gonzalez Somermeyer L.,
RA Gorokhovatsky A.Y., Vvedensky A., Purtov K.V., Petushkov V.N.,
RA Rodionova N.S., Chepurnyh T.V., Fakhranurova L.I., Guglya E.B.,
RA Ziganshin R., Tsarkova A.S., Kaskova Z.M., Shender V., Abakumov M.,
RA Abakumova T.O., Povolotskaya I.S., Eroshkin F.M., Zaraisky A.G.,
RA Mishin A.S., Dolgov S.V., Mitiouchkina T.Y., Kopantzev E.P.,
RA Waldenmaier H.E., Oliveira A.G., Oba Y., Barsova E., Bogdanova E.A.,
RA Gabaldon T., Stevani C.V., Lukyanov S., Smirnov I.V., Gitelson J.I.,
RA Kondrashov F.A., Yampolsky I.V.;
RT "Genetically encodable bioluminescent system from fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:12728-12732(2018).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26094784; DOI=10.1002/anie.201501779;
RA Purtov K.V., Petushkov V.N., Baranov M.S., Mineev K.S., Rodionova N.S.,
RA Kaskova Z.M., Tsarkova A.S., Petunin A.I., Bondar V.S., Rodicheva E.K.,
RA Medvedeva S.E., Oba Y., Oba Y., Arseniev A.S., Lukyanov S., Gitelson J.I.,
RA Yampolsky I.V.;
RT "The chemical basis of fungal bioluminescence.";
RL Angew. Chem. Int. Ed. 54:8124-8128(2015).
CC -!- FUNCTION: Hispidin-3-hydroxylase; part of the gene cluster that
CC mediates the fungal bioluminescence cycle (PubMed:30478037,
CC PubMed:26094784). Hydroxylates hispidin in order to produce the fungal
CC luciferin 3-hydroxyhispidin (PubMed:30478037, PubMed:26094784). The
CC fungal bioluminescence cycle begins with the hispidin synthetase that
CC catalyzes the formation of hispidin which is further hydroxylated by
CC the hispidin-3-hydroxylase, yielding the fungal luciferin 3-
CC hydroxyhispidin. The luciferase then produces an endoperoxide as a
CC high-energy intermediate with decomposition that yields oxyluciferin
CC (also known as caffeoylpyruvate) and light emission. Oxyluciferin can
CC be recycled to caffeic acid by caffeoylpyruvate hydrolase
CC (PubMed:30478037) (Probable). {ECO:0000269|PubMed:26094784,
CC ECO:0000269|PubMed:30478037, ECO:0000305|PubMed:30478037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hispidin + NADH + O2 = 3-hydroxyhispidin + H2O +
CC NAD(+); Xref=Rhea:RHEA:71115, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:190288, ChEBI:CHEBI:190289;
CC Evidence={ECO:0000250|UniProtKB:A0A146I0C4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71116;
CC Evidence={ECO:0000250|UniProtKB:A0A146I0C4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hispidin + NADPH + O2 = 3-hydroxyhispidin + H2O +
CC NADP(+); Xref=Rhea:RHEA:71119, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:190288, ChEBI:CHEBI:190289;
CC Evidence={ECO:0000269|PubMed:26094784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71120;
CC Evidence={ECO:0000269|PubMed:26094784};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30478037}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:A0A146I0C4}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: The availability of a complete eukaryotic luciferin
CC biosynthesis pathway provides several applications in biomedicine and
CC bioengineering. {ECO:0000269|PubMed:30478037}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000269|PubMed:30478037, ECO:0000305}.
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DR EMBL; LC435367; BBH43497.1; -; mRNA.
DR SMR; A0A3G9K5C8; -.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Membrane; Monooxygenase; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..422
FT /note="Hispidin-3-hydroxylase"
FT /id="PRO_0000455706"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 18
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 37..38
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 247..249
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 318
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 328..332
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 422 AA; 46449 MW; 3CE9DAD13C0E4A57 CRC64;
Query Match 100.0%; Score 2185; DB 1; Length 422;
Best Local Similarity 100.0%;
Matches 422; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MASFENSLSVLIVGAGLGGLAAAIA LRRQGHVVKIYDSSSFKAELGAGLAVPPNTLRSLQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MASFENSLSVLIVGAGLGGLAAAIA LRRQGHVVKIYDSSSFKAELGAGLAVPPNTLRSLQ 60
Qy 61 QLGCNTENLNGVDNLCFTAMGYDGSVGMMNNMTDYREAYGTSWIMVHRVDLHNELMRVAL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 QLGCNTENLNGVDNLCFTAMGYDGSVGMMNNMTDYREAYGTSWIMVHRVDLHNELMRVAL 120
Qy 121 DPGGLGPPATLHLNHRVTFCDVDACTVTFTNGTTQSADLIVGADGIRSTIRRFVLEEDVT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DPGGLGPPATLHLNHRVTFCDVDACTVTFTNGTTQSADLIVGADGIRSTIRRFVLEEDVT 180
Qy 181 VPASGIVGFRWLVQADALDPYPELDWIVKKPPLGARLISTPQNPQSGVGLADRRTIIIYA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VPASGIVGFRWLVQADALDPYPELDWIVKKPPLGARLISTPQNPQSGVGLADRRTIIIYA 240
Qy 241 CRGGTMVNVLAVHDDERDQNTADWSVPASKDDLFRVFHDYHPRFRRLLELAQDINLWQMR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CRGGTMVNVLAVHDDERDQNTADWSVPASKDDLFRVFHDYHPRFRRLLELAQDINLWQMR 300
Qy 301 VVPVLKKWVNKRVCLLGDAAHASLPTLGQGFGMGLEDAVALGTLLPKGTTASQIETRLAV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VVPVLKKWVNKRVCLLGDAAHASLPTLGQGFGMGLEDAVALGTLLPKGTTASQIETRLAV 360
Qy 361 YEQLRKDRAEFVAAESYEEQYVPEMRGLYLRSKELRDRVMGYDIKVESEKVLETLLRSSN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 YEQLRKDRAEFVAAESYEEQYVPEMRGLYLRSKELRDRVMGYDIKVESEKVLETLLRSSN 420
Qy 421 SA 422
||
Db 421 SA 422
ALIGNMENT: SEQ ID NO:35
RESULT 1
HIPS_NEONM
ID HIPS_NEONM Reviewed; 1678 AA.
AC A0A3G9K3K9;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 12-OCT-2022, entry version 17.
DE RecName: Full=Hispidin synthase {ECO:0000303|PubMed:30478037};
DE Short=HispS {ECO:0000303|PubMed:30478037};
DE EC=2.3.1.- {ECO:0000269|PubMed:30478037};
DE AltName: Full=Fungal bioluminescence cycle protein hips {ECO:0000303|PubMed:30478037};
DE AltName: Full=PKS-NRPS hybrid synthetase hips {ECO:0000303|PubMed:30478037};
GN Name=hisps {ECO:0000303|PubMed:30478037};
OS Neonothopanus nambi (Agaricus nambi).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Omphalotaceae; Neonothopanus.
OX NCBI_TaxID=71958;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION, FUNCTION, DOMAIN, CATALYTIC
RP ACTIVITY, PATHWAY, AND BIOTECHNOLOGY.
RX PubMed=30478037; DOI=10.1073/pnas.1803615115;
RA Kotlobay A.A., Sarkisyan K.S., Mokrushina Y.A., Marcet-Houben M.,
RA Serebrovskaya E.O., Markina N.M., Gonzalez Somermeyer L.,
RA Gorokhovatsky A.Y., Vvedensky A., Purtov K.V., Petushkov V.N.,
RA Rodionova N.S., Chepurnyh T.V., Fakhranurova L.I., Guglya E.B.,
RA Ziganshin R., Tsarkova A.S., Kaskova Z.M., Shender V., Abakumov M.,
RA Abakumova T.O., Povolotskaya I.S., Eroshkin F.M., Zaraisky A.G.,
RA Mishin A.S., Dolgov S.V., Mitiouchkina T.Y., Kopantzev E.P.,
RA Waldenmaier H.E., Oliveira A.G., Oba Y., Barsova E., Bogdanova E.A.,
RA Gabaldon T., Stevani C.V., Lukyanov S., Smirnov I.V., Gitelson J.I.,
RA Kondrashov F.A., Yampolsky I.V.;
RT "Genetically encodable bioluminescent system from fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:12728-12732(2018).
CC -!- FUNCTION: PKS-NRPS hybrid synthetase; part of the gene cluster that
CC mediates the fungal bioluminescence cycle (PubMed:30478037). Performs
CC the biosynthesis of hispidin from caffeic acid by two cycles of
CC addition of malonyl units followed by lactonization (PubMed:30478037).
CC The fungal bioluminescence cycle begins with the hispidin synthetase
CC that catalyzes the formation of hispidin which is further hydroxylated
CC by the hispidin-3-hydroxylase, yielding the fungal luciferin 3-
CC hydroxyhispidin. The luciferase then produces an endoperoxide as a
CC high-energy intermediate with decomposition that yields oxyluciferin
CC (also known as caffeoylpyruvate) and light emission. Oxyluciferin can
CC be recycled to caffeic acid by caffeoylpyruvate hydrolase
CC (PubMed:30478037) (Probable). {ECO:0000269|PubMed:30478037,
CC ECO:0000305|PubMed:30478037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-caffeate + ATP + H(+) + 2 malonyl-CoA = AMP + 2 CO2 + 2
CC CoA + diphosphate + hispidin; Xref=Rhea:RHEA:71123,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57770, ChEBI:CHEBI:190288, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:30478037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71124;
CC Evidence={ECO:0000269|PubMed:30478037};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30478037}.
CC -!- DOMAIN: The architecture of hips is the following one: adenylation (A),
CC phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS)
CC and malonyl-CoA:ACP transacylase (MAT). Hips homologs in bioluminescent
CC species lack two domains, the ketoreductase (KR) and the dehydratase
CC (DH) domains. {ECO:0000305|PubMed:30478037}.
CC -!- BIOTECHNOLOGY: The availability of a complete eukaryotic luciferin
CC biosynthesis pathway provides several applications in biomedicine and
CC bioengineering. {ECO:0000269|PubMed:30478037}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; LC435355; BBH43485.1; -; mRNA.
DR SMR; A0A3G9K3K9; -.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
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; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 2.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..1678
FT /note="Hispidin synthase"
FT /id="PRO_0000455704"
FT DOMAIN 586..661
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1597..1672
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 33..453
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30478037"
FT REGION 686..1111
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30478037"
FT REGION 1201..1499
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30478037"
FT REGION 1562..1582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1562..1578
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 620
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1632
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1678 AA; 180756 MW; 665A86328C20F389 CRC64;
Query Match 100.0%; Score 8568; DB 1; Length 1678;
Best Local Similarity 100.0%;
Matches 1678; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNSSKNPPSTLLDVFLDTARNLDTALRNVLECGEHRWSYRELDTVSSALAQHLRYTVGLS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNSSKNPPSTLLDVFLDTARNLDTALRNVLECGEHRWSYRELDTVSSALAQHLRYTVGLS 60
Qy 61 PTVAVISENHPYILALMLAVWKLGGTFAPIDVHSPAELVAGMLNIVSPSCLVIPSSDVTN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PTVAVISENHPYILALMLAVWKLGGTFAPIDVHSPAELVAGMLNIVSPSCLVIPSSDVTN 120
Qy 121 QTLACDLNIPVVAFHPHQSTIPELNKKYLTDSQISPDLPFSDPNRPALYLFTSSATSRSN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QTLACDLNIPVVAFHPHQSTIPELNKKYLTDSQISPDLPFSDPNRPALYLFTSSATSRSN 180
Qy 181 LKCVPLTHTFILRNSLSKRAWCKRMRPETDFDGIRVLGWAPWSHVLAHMQDIGPLTLLNA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LKCVPLTHTFILRNSLSKRAWCKRMRPETDFDGIRVLGWAPWSHVLAHMQDIGPLTLLNA 240
Qy 241 GCYVFATTPSTYPTELKDDRDLISCAANAIMYKGVKSFACLPFVLGGLKALCESEPSVKA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GCYVFATTPSTYPTELKDDRDLISCAANAIMYKGVKSFACLPFVLGGLKALCESEPSVKA 300
Qy 301 HLQVEERAQLLKSLQHMEILECGGAMLEASVASWAIENCIPISIGIGMTETGGALFAGPV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 HLQVEERAQLLKSLQHMEILECGGAMLEASVASWAIENCIPISIGIGMTETGGALFAGPV 360
Qy 361 QAIKTGFSSEDKFIEDATYLLVKDDHESHAEEDINEGELVVKSKMLPRGYLGYSDPSFSV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QAIKTGFSSEDKFIEDATYLLVKDDHESHAEEDINEGELVVKSKMLPRGYLGYSDPSFSV 420
Qy 421 DDAGWVTFRTGDRYSVTPDGKFSWLGRNTDFIQMTSGETLDPRPIESSLCESSLISRACV 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DDAGWVTFRTGDRYSVTPDGKFSWLGRNTDFIQMTSGETLDPRPIESSLCESSLISRACV 480
Qy 481 IGDKFLNGPAAAVCAIIELEPTAVEKGQAHSREIARVFAPINRDLPPPLRIAWSHVLVLQ 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 IGDKFLNGPAAAVCAIIELEPTAVEKGQAHSREIARVFAPINRDLPPPLRIAWSHVLVLQ 540
Qy 541 PSEKIPMTKKGTIFRKKIEQVFGSALGGSSGDNSQATADAGVVRRDELSNTVKHIISRVL 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 PSEKIPMTKKGTIFRKKIEQVFGSALGGSSGDNSQATADAGVVRRDELSNTVKHIISRVL 600
Qy 601 GVSDDELLWTLSFAELGMTSALATRIANELNEVLVGVNLPINACYIHVDLPSLSNAVYAK 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GVSDDELLWTLSFAELGMTSALATRIANELNEVLVGVNLPINACYIHVDLPSLSNAVYAK 660
Qy 661 LAHLKLPDRTPEPRQAPVENSGGKEIVVVGQAFRLPGSINDVASLRDAFLARQASSIITE 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 LAHLKLPDRTPEPRQAPVENSGGKEIVVVGQAFRLPGSINDVASLRDAFLARQASSIITE 720
Qy 721 IPSDRWDHASFYPKDIRFNKAGLVDIANYDHSFFGLTATEALYLSPTMRLALEVSFEALE 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 IPSDRWDHASFYPKDIRFNKAGLVDIANYDHSFFGLTATEALYLSPTMRLALEVSFEALE 780
Qy 781 NANIPVSQLKGSQTAVYVATTDDGFETLLNAEAGYDAYTRFYGTGRAASTASGRISCLLD 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 NANIPVSQLKGSQTAVYVATTDDGFETLLNAEAGYDAYTRFYGTGRAASTASGRISCLLD 840
Qy 841 VHGPSITVDTACSGGAVCIDQAIDYLQSSSAADTAIICASNTHCWPGSFRFLSAQGMVSP 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 VHGPSITVDTACSGGAVCIDQAIDYLQSSSAADTAIICASNTHCWPGSFRFLSAQGMVSP 900
Qy 901 GGRCATFTTDADGYVPSEGAVAFILKTREAAMRDKDTILATIKATQISHNGRSQGLVAPN 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GGRCATFTTDADGYVPSEGAVAFILKTREAAMRDKDTILATIKATQISHNGRSQGLVAPN 960
Qy 961 VNSQADLHRSLLQKAGLSPADIRFIEAHGTGTSLGDLSEIQAINDAYTSSQPRTTGPLIV 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 VNSQADLHRSLLQKAGLSPADIRFIEAHGTGTSLGDLSEIQAINDAYTSSQPRTTGPLIV 1020
Qy 1021 SASKTVIGHTEPAGPLVGMLSVLNSFKEGAVPGLAHLTADNLNPSLDCSSVPLLIPYQPV 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SASKTVIGHTEPAGPLVGMLSVLNSFKEGAVPGLAHLTADNLNPSLDCSSVPLLIPYQPV 1080
Qy 1081 HLAAPKPHRAAVRSYGFSGTLGGIVLEAPDEERLEEELPNDKPMLFVVSAKTHTALIEYL 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 HLAAPKPHRAAVRSYGFSGTLGGIVLEAPDEERLEEELPNDKPMLFVVSAKTHTALIEYL 1140
Qy 1141 GRYLEFLLQANPQDFCDICYTSCVGREHYRYRYACVANDMEDLIGQLQKRLGSKVPPKPS 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GRYLEFLLQANPQDFCDICYTSCVGREHYRYRYACVANDMEDLIGQLQKRLGSKVPPKPS 1200
Qy 1201 YKRGALAFAFSGQGTQFRGMATELAKAYSGFRKIVSDLAKRASELSGHAIDRFLLAYDIG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 YKRGALAFAFSGQGTQFRGMATELAKAYSGFRKIVSDLAKRASELSGHAIDRFLLAYDIG 1260
Qy 1261 AENVAPDSEADQICIFVYQCSVLRWLQTMGIRPSAVIGHSLGEISASVAAGALSLDSALD 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 AENVAPDSEADQICIFVYQCSVLRWLQTMGIRPSAVIGHSLGEISASVAAGALSLDSALD 1320
Qy 1321 LVISRARLLRSSASAPAGMAAMSASQDEVVELIGKLDLDKANSLSVSVINGPQNTVVSGS 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 LVISRARLLRSSASAPAGMAAMSASQDEVVELIGKLDLDKANSLSVSVINGPQNTVVSGS 1380
Qy 1381 SAAIESIVALAKGRKIKASALNINQAFHSPYVDSAVPGLRAWSEKHISSARPLQIPLYST 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 SAAIESIVALAKGRKIKASALNINQAFHSPYVDSAVPGLRAWSEKHISSARPLQIPLYST 1440
Qy 1441 LLGAQISEGEMLNPDHWVDHARKPVQFAQAATTMKESFTGVIIDIGPQVVAWSLLLSNGL 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 LLGAQISEGEMLNPDHWVDHARKPVQFAQAATTMKESFTGVIIDIGPQVVAWSLLLSNGL 1500
Qy 1501 TSVTALAAKRGRSQQVAFLSALADLYQDYGVVPDFVGLYAQQEDASRLKKTDILTYPFQR 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 TSVTALAAKRGRSQQVAFLSALADLYQDYGVVPDFVGLYAQQEDASRLKKTDILTYPFQR 1560
Qy 1561 GEETLSSGSSTPTLENTDLDSGKELLMGPTRGLLRADDLRDSIVSSVKDVLELKSNEDLD 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 GEETLSSGSSTPTLENTDLDSGKELLMGPTRGLLRADDLRDSIVSSVKDVLELKSNEDLD 1620
Qy 1621 LSESLNALGMDSIMFAQLRKRIGEGLGLNVPMVFLSDAFSIGEMVSNLVEQAEASEDN 1678
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 LSESLNALGMDSIMFAQLRKRIGEGLGLNVPMVFLSDAFSIGEMVSNLVEQAEASEDN 1678
ALIGNMENT: SEQ ID NO:65
RESULT 1
CPH_NEONM
ID CPH_NEONM Reviewed; 289 AA.
AC A0A3G9JYJ6;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Caffeoylpyruvate hydrolase {ECO:0000303|PubMed:30478037};
DE Short=CPH {ECO:0000303|PubMed:30478037};
DE EC=3.7.-.- {ECO:0000269|PubMed:28508049};
DE AltName: Full=Fungal bioluminescence cycle protein cph {ECO:0000303|PubMed:30478037};
GN Name=cph {ECO:0000303|PubMed:30478037};
OS Neonothopanus nambi (Agaricus nambi).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Omphalotaceae; Neonothopanus.
OX NCBI_TaxID=71958;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION, FUNCTION, PATHWAY, AND
RP BIOTECHNOLOGY.
RX PubMed=30478037; DOI=10.1073/pnas.1803615115;
RA Kotlobay A.A., Sarkisyan K.S., Mokrushina Y.A., Marcet-Houben M.,
RA Serebrovskaya E.O., Markina N.M., Gonzalez Somermeyer L.,
RA Gorokhovatsky A.Y., Vvedensky A., Purtov K.V., Petushkov V.N.,
RA Rodionova N.S., Chepurnyh T.V., Fakhranurova L.I., Guglya E.B.,
RA Ziganshin R., Tsarkova A.S., Kaskova Z.M., Shender V., Abakumov M.,
RA Abakumova T.O., Povolotskaya I.S., Eroshkin F.M., Zaraisky A.G.,
RA Mishin A.S., Dolgov S.V., Mitiouchkina T.Y., Kopantzev E.P.,
RA Waldenmaier H.E., Oliveira A.G., Oba Y., Barsova E., Bogdanova E.A.,
RA Gabaldon T., Stevani C.V., Lukyanov S., Smirnov I.V., Gitelson J.I.,
RA Kondrashov F.A., Yampolsky I.V.;
RT "Genetically encodable bioluminescent system from fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:12728-12732(2018).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28508049; DOI=10.1126/sciadv.1602847;
RA Kaskova Z.M., Doerr F.A., Petushkov V.N., Purtov K.V., Tsarkova A.S.,
RA Rodionova N.S., Mineev K.S., Guglya E.B., Kotlobay A., Baleeva N.S.,
RA Baranov M.S., Arseniev A.S., Gitelson J.I., Lukyanov S., Suzuki Y.,
RA Kanie S., Pinto E., Di Mascio P., Waldenmaier H.E., Pereira T.A.,
RA Carvalho R.P., Oliveira A.G., Oba Y., Bastos E.L., Stevani C.V.,
RA Yampolsky I.V.;
RT "Mechanism and color modulation of fungal bioluminescence.";
RL Sci. Adv. 3:e1602847-e1602847(2017).
CC -!- FUNCTION: Caffeoylpyruvate hydrolase; part of the gene cluster that
CC mediates the fungal bioluminescence cycle (PubMed:30478037,
CC PubMed:28508049). Involved in the recycling of oxyluciferin, a pyruvic
CC acid adduct of caffeic acid, to caffeic acid (PubMed:30478037,
CC PubMed:28508049). The fungal bioluminescence cycle begins with the
CC hispidin synthetase that catalyzes the formation of hispidin which is
CC further hydroxylated by the hispidin-3-hydroxylase, yielding the fungal
CC luciferin 3-hydroxyhispidin. The luciferase then produces an
CC endoperoxide as a high-energy intermediate with decomposition that
CC yields oxyluciferin (also known as caffeoylpyruvate) and light
CC emission. Oxyluciferin can be recycled to caffeic acid by
CC caffeoylpyruvate hydrolase (PubMed:30478037) (Probable).
CC {ECO:0000269|PubMed:28508049, ECO:0000269|PubMed:30478037,
CC ECO:0000305|PubMed:30478037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-caffeoylpyruvate + H2O = (E)-caffeate + H(+) + pyruvate;
CC Xref=Rhea:RHEA:71155, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57770, ChEBI:CHEBI:190290;
CC Evidence={ECO:0000269|PubMed:28508049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71156;
CC Evidence={ECO:0000269|PubMed:28508049};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q6P587};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q6P587};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30478037}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6P587}.
CC -!- BIOTECHNOLOGY: The availability of a complete eukaryotic luciferin
CC biosynthesis pathway provides several applications in biomedicine and
CC bioengineering. {ECO:0000269|PubMed:30478037}.
CC -!- SIMILARITY: Belongs to the FAH family. {ECO:0000305}.
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DR EMBL; LC435389; BBH43519.1; -; mRNA.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.90.850.10; -; 1.
DR InterPro; IPR011234; Fumarylacetoacetase-like_C.
DR InterPro; IPR036663; Fumarylacetoacetase_C_sf.
DR Pfam; PF01557; FAA_hydrolase; 1.
DR SUPFAM; SSF56529; SSF56529; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Magnesium; Metal-binding.
FT CHAIN 1..289
FT /note="Caffeoylpyruvate hydrolase"
FT /id="PRO_0000455705"
FT BINDING 140
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q6P587"
FT BINDING 142
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q6P587"
FT BINDING 171
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q6P587"
SQ SEQUENCE 289 AA; 31419 MW; FDF0501E5CC6D535 CRC64;
Query Match 100.0%; Score 1473; DB 1; Length 289;
Best Local Similarity 100.0%;
Matches 289; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAPISSTWSRLIRFVAIETSLVHIGEPIDATMDVGLARREGKTIQAYEIIGSGSALDLSA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAPISSTWSRLIRFVAIETSLVHIGEPIDATMDVGLARREGKTIQAYEIIGSGSALDLSA 60
Qy 61 QVSKNVLTVRELLMPLSREEIKTVRCLGLNYPVHATEANVAVPKFPNLFYKPVTSLIGPD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 QVSKNVLTVRELLMPLSREEIKTVRCLGLNYPVHATEANVAVPKFPNLFYKPVTSLIGPD 120
Qy 121 GLITIPSVVQPPKEHQSDYEAELVIVIGKAAKNVSEDEALDYVLGYTAANDISFRKHQLA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GLITIPSVVQPPKEHQSDYEAELVIVIGKAAKNVSEDEALDYVLGYTAANDISFRKHQLA 180
Qy 181 VSQWSFSKGFGSLLLTIRMAQTHSGNINRFSRDQIFNVKKTISFLSQGTTLEPGSIILTG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VSQWSFSKGFGSLLLTIRMAQTHSGNINRFSRDQIFNVKKTISFLSQGTTLEPGSIILTG 240
Qy 241 TPDGVGFVRNPPLYLKDGDEVMTWIGSGIGTLANTVQEEKTCFASGGHE 289
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TPDGVGFVRNPPLYLKDGDEVMTWIGSGIGTLANTVQEEKTCFASGGHE 289
Conclusion
14. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
Prosecution Insights