Transformant and method for producing m-aminophenol using the same

Abstract

To provide a transformant capable of biologically producing m-aminophenols.SOLUTION: In one aspect, the present invention relates to a transformant for producing m-aminophenols, which is obtained by expressibly introducing (A) genes encoding enzymes having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxy benzoate and (B) genes encoding enzymes having an activity of decarboxylating 2-amino-4-hydroxy benzoic acids into a microbial host having an ability to produce anthranilic acid. In another aspect, the present invention relates to a transformant for producing P450 reductase, which is obtained by expressibly introducing cyp genes encoding cytochrome P450, cpr genes encoding cytochrome P450 reductase, and ubiD genes or sdc genes encoding decarboxylase into microbial hosts capable of producing anthranilic acid.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present disclosure relates to techniques for producing m-aminophenol. In one aspect, the present disclosure relates to a transformant that has been subjected to a specific genetic manipulation, and a technique for producing m-aminophenol using the transformant. [Background technology]

[0002] m-Aminophenol (CAS number: 591-27-5. Synonyms include 3-aminophenol, 3-amino-1-hydroxybenzene, and 3-hydroxyaniline) is an aromatic compound used as a raw material for aramid fibers. Anthranilic acid (CAS number: 118-92-3; synonyms include anthranilate and 2-aminobenzoic acid), which is a precursor of m-aminophenol, can also be produced from sugars by fermentation using microorganisms (for example, Patent Document 1 and Patent Document 2). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 5-94 [Patent Document 2] Special Publication No. 6-500695 Summary of the Invention [Problem to be solved by the invention]

[0004] The present disclosure provides a transformant capable of biologically producing m-aminophenol, and a method for producing m-aminophenol using the transformant. [Means for solving the problem]

[0005] In one aspect, the present disclosure relates to a transformant for producing m-aminophenol, which is obtained by expressibly introducing a gene (A) encoding an enzyme having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, and a gene (B) encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity into a microbial host capable of producing anthranilic acid.

[0006] In another aspect, the present disclosure relates to a transformant for producing m-aminophenol, which is obtained by expressibly introducing a cyp gene encoding cytochrome P450, a cpr gene encoding cytochrome P450 reductase, and an ubiD gene or an sdc gene encoding a decarboxylase into a microbial host capable of producing anthranilic acid.

[0007] In another aspect, the present disclosure relates to a method for producing m-aminophenol, comprising the step of culturing the transformant of the present disclosure to produce m-aminophenol. Effect of the Invention

[0008] According to the present disclosure, it is possible to provide a new transformant capable of biologically producing m-aminophenol using sugars as a raw material, and a method for producing m-aminophenol using the transformant. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a diagram showing a schematic diagram of m-aminophenol production in the transformant of the present disclosure. [Diagram 2] FIG. 2 is an overall metabolic pathway diagram illustrating the biosynthetic pathway of m-aminophenol in one embodiment of the transformant of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present disclosure is based on the discovery by the present inventors that a transformant capable of biologically producing m-aminophenol using sugars as a raw material can be obtained by expressing a gene (A) encoding an enzyme having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid and a gene (B) encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity into a microbial host capable of producing anthranilic acid. In addition, the present disclosure is based on the discovery by the present inventors that a transformant capable of biologically producing m-aminophenol using sugars as raw materials can be obtained by expressing a cyp gene encoding cytochrome P450, a cpr gene encoding cytochrome P450 reductase (abbreviated as CYP reductase; EC number: EC 1.6.2.4), and an ubiD gene or an sdc gene encoding a decarboxylase into a microbial host capable of producing anthranilic acid.

[0011] In the present disclosure, in one or more embodiments, "introduction of a gene" refers to introduction of the gene so that the gene can be expressed in a host. In one or more embodiments, gene introduction into a host can be performed using a general gene recombination technique (for example, the method described in Michael R. Green & Joseph Sambrook, Molecular cloning, Cold Spring Harbor Laboratory Press). In one or more embodiments, examples of gene introduction include gene introduction using a plasmid vector, or incorporation into the chromosome of a microbial host.

[0012] In the present disclosure, "90% or more identity" with respect to an amino acid sequence or a nucleotide sequence means at least 90% identity, and in one or more embodiments, means 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity.

[0013] In the present disclosure, "identity of amino acid sequence or nucleotide sequence" can be performed using a readily available sequence comparison computer program. In one or more embodiments, the computer program may include the GCG Wisconsin Bestfit package (University of Wisconsin, USA; Devereux et al. (1984) Nucleic Acids Res. 12: 387), the BLAST package (Ausubel et al. (1999) ibid-Ch. 18), and FASTA (Atschul et al. (1990) J. Mol. Biol. 403-410).

[0014] In the present disclosure, "stringent conditions" refers to conditions under which so-called specific hybrids are formed and non-specific hybrids are not formed. In one or more embodiments, stringent conditions include conditions under which highly identical base sequences hybridize with each other, but base sequences with lower identity do not hybridize with each other. In one or more embodiments, high identity between base sequences includes identity of 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, or 97% or more. In one or more embodiments, stringent conditions may be conditions described in Molecular Cloning, A Laboratory Manual, Second Edition, 1989, Vol2, p11.45. Specifically, hybridization may occur at a temperature 5 to 10°C lower than the melting temperature (Tm) of a complete hybrid.

[0015] [Transformants] The present disclosure relates to a transformant for producing m-aminophenol. Specifically, the transformant according to the present disclosure, in one embodiment, is a transformant for producing m-aminophenol, which can be obtained by expressibly introducing the above-mentioned gene (A) and gene (B) into a microbial host capable of producing anthranilic acid. Also, the transformant according to the present disclosure, in one embodiment, is a transformant for producing m-aminophenol, which can be obtained by expressibly introducing the cyp gene, the cpr gene, and the ubiD gene or the sdc gene into a microbial host capable of producing anthranilic acid. As shown in Fig. 1, the transformant according to the present disclosure can produce anthranilic acid from sugars in the living body of the transformant, and can produce m-aminophenol from anthranilic acid by gene (A) and gene (B). In one or more embodiments, the cyp gene can be used as the gene (A) to be introduced, and it is preferable to use the cyp gene and the cpr gene. In one or more embodiments, the ubiD gene or the sdc gene can be used as the gene (B) to be introduced.

[0016] [Microbial host capable of producing anthranilic acid] In the present disclosure, the term "microbial host capable of producing anthranilic acid" refers to a microbial host capable of expressing at least an enzyme having anthranilate synthase activity. The microbial host according to the present disclosure may be not only a bacterium having a gene encoding an enzyme having anthranilate synthase activity as a wild type, but also a bacterium artificially transformed so as to be capable of expressing an enzyme having anthranilate synthase activity. In one or more embodiments, the microbial host capable of producing anthranilic acid may be a bacterium having a gene encoding an enzyme having anthranilate synthase activity as a wild type, transformed in a state capable of expressing an enzyme having anthranilate synthase activity. In one or more embodiments, the microbial host capable of producing anthranilic acid is preferably a bacterium into which a gene encoding an enzyme having anthranilate synthase activity has been introduced by genetic modification, from the viewpoint of improving m-aminophenol productivity. The enzyme having anthranilate synthase activity refers to an enzyme having an activity of catalyzing a reaction for synthesizing anthranilate from chorismic acid. Whether or not an enzyme having anthranilate synthase activity is expressed in the microorganism can be confirmed, for example, by adding the microbial cells or a cell disruption solution to a reaction solution containing chorismic acid and glutamine, and analyzing whether or not anthranilic acid is produced. In one or more embodiments, the analysis of the production of anthranilic acid can be performed by an appropriate method such as high performance liquid chromatography. In one or more embodiments, the microbial host according to the present disclosure may be a microbial host in which the expression level of an enzyme having anthranilate synthase activity is improved from the viewpoint of improving the productivity of m-aminophenol, a microbial host that overexpresses an enzyme having anthranilate synthase activity or is capable of improving the expression level or inducing the overexpression, etc. The expression level of the enzyme can be adjusted or improved by a person skilled in the art, as appropriate, for example, by using a suitable promoter.

[0017] In one or more embodiments, the gene encoding the enzyme having anthranilate synthase activity includes the trpEG gene, etc., preferably the trpEG gene derived from Corynebacterium glutamicum. In one or more embodiments, the trpEG gene derived from Corynebacterium glutamicum includes a gene consisting of the base sequence shown in SEQ ID NO: 140. In one or more embodiments, the gene encoding the enzyme having anthranilate synthase activity includes a gene containing a base sequence having an identity of 80% or more, 85% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 100% to SEQ ID NO: 140, or a gene consisting of said base sequence.

[0018] In one or a plurality of embodiments, the transformant according to the present disclosure may further include a gene encoding an enzyme having anthranilate synthase activity, which is introduced into a microbial host capable of producing anthranilic acid.

[0019] The microbial host according to the present disclosure is not particularly limited, and may be, for example, a coryneform bacterium, Escherichia coli (bacteria of the genus Escherichia, particularly Escherichia coli), a solvent-tolerant bacterium, or a yeast. Coryneform bacteria are a group of microorganisms defined in Bergey's Manual of Determinative Bacteriology, Vol. 8, 599 (1974), and are not particularly limited as long as they grow under normal aerobic conditions. In one or more embodiments, the coryneform bacteria include bacteria of the genus Corynebacterium, Brevibacterium, Arthrobacter, Mycobacterium, and Micrococcus. In one or a plurality of embodiments, examples of the solvent-resistant bacteria include Pseudomonas putida S12, Pseudomonas aeruginosa, Pseudomonas paucimobilis, Pseudomonas alcaligenes, Pseudomonas fluorescens, Pseudomonas fragi, Pseudomonas oleovorans, Pseudomonas sp., Rhodococcus erythropolis, Rhodococcus opacus, Burkholderia cepacia, and Paenibacillus illinoisensis.

[0020] The microbial host according to the present disclosure is not particularly limited, and may be, for example, a bacterium of the genus Corynebacterium. In one or more embodiments, examples of the bacterium of the genus Corynebacterium include Corynebacterium glutamicum, Corynebacterium efficiens, Corynebacterium ammoniagenes, Corynebacterium halotolerance, and Corynebacterium alkanolyticum. The microbial host according to the present disclosure is not particularly limited, and may be, for example, Corynebacterium glutamicum.

[0021] The microbial host according to the present disclosure is not particularly limited, and may be, for example, Corynebacterium glutamicum R (FERM BP-18976), ATCC13032, or ATCC13869.

[0022] [Gene (A)] In the present disclosure, the gene (A) may be one type of gene or a combination of two or more types of genes in one or more embodiments. In one or more embodiments, the gene (A) encoding an enzyme having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid may be, but is not particularly limited to, a gene cyp encoding cytochrome P450, and from the viewpoint of improving the productivity of m-aminophenol, it is preferable to have at least the gene cyp and the gene cpr encoding cytochrome P450 reductase (abbreviation: CYP reductase; EC number: EC 1.6.2.4). In one or more embodiments, a polypeptide encoded by the cyp gene (e.g., cytochrome P450, etc.) may have an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid in combination with a polypeptide encoded by the cpr gene (e.g., cytochrome P450 reductase, etc.).

[0023] In one or more embodiments, from the viewpoint of improving the productivity of m-aminophenol, it is also preferable to express the polypeptide encoded by the cyp gene in cells together with the polypeptide encoded by the cpr gene. Most of the polypeptides encoded by the cyp gene are polypeptides consisting of about 500 amino acid residues, and are a type of hemoprotein having heme at the active site. The polypeptide encoded by the cyp gene supplies oxygen atoms to the reaction substrate using oxygen and electrons transferred from iron in the active center and nicotinamide adenine dinucleotide phosphate (NADPH) via the electron transport system. The electron transport system here refers to the polypeptide encoded by the cpr gene.

[0024] The polypeptide encoded by the cpr gene is known as a protein that requires two flavin molecules, namely flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), as cofactors. The polypeptide encoded by the cpr gene generally has a membrane-binding region, an FAD domain, and an FMN domain, and transfers electrons donated by NADPH to a heme protein via FAD and FMN in sequence. In this case, the target to which electrons are transferred is a polypeptide encoded by the cyp gene.

[0025] Polypeptides encoded by cyp genes have high substrate specificity and may exist in multiple types within a cell. Polypeptides encoded by cpr genes are known to function as targets for polypeptides encoded by various types of cyp genes.

[0026] The origin of the cyp gene and the cpr gene is as described below. In one or more embodiments, the cyp gene and the cpr gene may be introduced in combination from the same genus (or species), but it is not necessary to introduce the cyp gene and the cpr gene from the same genus (or species) in combination. Even when the cyp gene and the cpr gene from any different genera (or species) are introduced in combination into the host, the polypeptide encoded by the cyp gene can have the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid in combination with the polypeptide encoded by the cpr gene. The names (designations) of the "genus" and "species" of the organisms from which the genes are derived shown in the present disclosure are merely examples, and there may be synonymous alternative names.

[0027] [cyp gene] The origin of the cyp gene is not particularly limited, and examples thereof include the genera Aspergillus, Cochliobolus, Phanerochaete, Neurospora, and Rhodotorula. Aspergillus species, in one or more embodiments, Aspergillus clavatus, Aspergillus niger, Aspergillus oryzae, Aspergillus fumigatus, Aspergillus phoencis, Aspergillus tubingensis, Aspergillus luchuensis, Aspergillus brasiliensis, Aspergillus piperis, Aspergillus costaricaensis, Aspergillus eucalypticola, Aspergillus vadensis, Aspergillus welwitschiae, Aspergillus ibericus, Aspergillus sclerotioniger, Aspergillus carbonarius, Aspergillus sclerotiicarbonarius, Aspergillus homomorphus, Aspergillus brunneoviolaceus, Aspergillus fijiensis, Aspergillus japonicus, Aspergillus uvarum, Aspergillus nomiae, Aspergillus parasiticus, Aspergillus tamarii, Aspergillus turcosus, Aspergillus caelatus, Aspergillus pseudotamarii, Aspergillus lentulus, Aspergillus udagawae, Aspergillus viridinutans, Aspergillus pseudoviridinutans, Aspergillus fumigatiaffinis, Aspergillus ochraceoroseus, Aspergillus wentii, Aspergillus melleus, Aspergillus hiratsukae, Aspergillus felis, Aspergillus rambellii, Aspergillus arachidicola, Aspergillus thermomutatus, Aspergillusfischeri, Aspergillus terreus, Aspergillus puulaauensis, Aspergillus nidulans, Aspergillus calidoustus, and Aspergillus tanneri. Examples of the cyp gene derived from Aspergillus clavatus include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 1, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 72. Examples of the cyp gene derived from Aspergillus niger include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 13, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 76. In one or more embodiments, examples of the genus Cochliobolus include Cochliobolus lunatus, Cochliobolus victoriae, Cochliobolus heterostrophus, Cochliobolus carbonum, Cochliobolus sativus, Cochliobolus miyabeanus, Cochliobolus kusanoi, and Cochliobolus spicifer. Examples of the cyp gene derived from Cochliobolus lunatus include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 4 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 73. In one or more embodiments, the genus Phanerochaete includes Phanerochaete chrysosporium, Phanerochaete sordida, and Phanerochaete carnosa. Examples of the cyp gene derived from Phanerochaete chrysosporium include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 7, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 74. The genus Phanerochaete is also synonymous with the genus Phanerodontia. In one or more embodiments, examples of the genus Neurospora include Neurospora crassa, Neurospora tetrasperm, Neurospora discreta, Neurospora intermedia, Neurospora sitophila, and Neurospora metzenbergii. Examples of the cyp gene derived from Neurospora crassa include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 10 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 75. In one or more embodiments, examples of the genus Rhodotorula include Rhodotorula minuta, Rhodotorula gracilis, Rhodotorula rubescens, Rhodotorula creatinivora, Rhodotorula diobovata, Rhodotorula bogoriensis, and Rhodotorula mucilaginosa. Examples of the cyp gene derived from Rhodotorula minuta include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 16 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 77.

[0028] The cyp gene is not particularly limited and may be, for example, any one of the following genes (A1), (A2), and (A3). (A1) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 72, 73, 74, 75, 76, or 77, or a gene encoding a polypeptide consisting of an amino acid sequence represented by SEQ ID NO: 72, 73, 74, 75, 76, or 77; (A2) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, 76, or 77, and encoding a polypeptide having an activity of hydroxylating anthranilic acid to generate 2-amino-4-hydroxybenzoic acid, or a gene encoding a polypeptide consisting of an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, 76, or 77, and encoding a polypeptide having an activity of hydroxylating anthranilic acid to generate 2-amino-4-hydroxybenzoic acid; (A3) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, 76 or 77, and that encodes a polypeptide having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, 76 or 77, and that encodes a polypeptide having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid. In one or more embodiments, the polypeptides encoded by the genes (A2) and (A3), in combination with the polypeptide encoded by the cpr gene, may exhibit activity to hydroxylate anthranilic acid to produce 2-amino-4-hydroxybenzoic acid.

[0029] The cyp gene is not particularly limited and may be, for example, any one of the following genes (A4), (A5), and (A6). (A4) a gene having a nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, 13, or 16, or a gene consisting of a nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, 13, or 16; (A5) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, 13, or 16, and encoding a polypeptide having activity to hydroxylate anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, or a gene consisting of a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, 13, or 16, and encoding a polypeptide having activity to hydroxylate anthranilic acid to produce 2-amino-4-hydroxybenzoic acid; (A6) A gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, 13 or 16 and encodes a polypeptide having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, or a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene consisting of the nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, 13 or 16 and encodes a polypeptide having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid. In one or more embodiments, the polypeptides encoded by the genes (A5) and (A6), in combination with the polypeptide encoded by the cpr gene, may exhibit activity to hydroxylate anthranilic acid to produce 2-amino-4-hydroxybenzoic acid.

[0030] In one or more embodiments, the cyp gene is preferably a cyp gene derived from Aspergillus clavatus, a cyp gene derived from Cochliobolus lunatus, a cyp gene derived from Phanerochaete chrysosporium, a cyp gene derived from Neurospora crassa, or a cyp gene derived from Aspergillus niger, from the viewpoint of improving the productivity of m-aminophenol. In the same respect, in one or more embodiments, the cyp gene is preferably a gene having a nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, or 13, or a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, or 76, and more preferably a gene consisting of the nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, or 13, or a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, or 76.

[0031] [cpr gene] The polypeptide encoded by the cpr gene is not particularly limited, and may have the function of donating electrons to the polypeptide encoded by the cyp gene to elicit the hydroxylation function of the polypeptide encoded by the cyp gene.

[0032] The origin of the cpr gene is not particularly limited, and examples thereof include the genera Aspergillus, Cochliobolus, Phanerochaete, Neurospora, and Rhodotorula. Aspergillus species, in one or more embodiments, Aspergillus clavatus, Aspergillus niger, Aspergillus oryzae, Aspergillus fumigatus, Aspergillus phoencis, Aspergillus tubingensis, Aspergillus luchuensis, Aspergillus brasiliensis, Aspergillus piperis, Aspergillus costaricaensis, Aspergillus eucalypticola, Aspergillus vadensis, Aspergillus welwitschiae, Aspergillus ibericus, Aspergillus sclerotioniger, Aspergillus carbonarius, Aspergillus sclerotiicarbonarius, Aspergillus homomorphus, Aspergillus brunneoviolaceus, Aspergillus fijiensis, Aspergillus japonicus, Aspergillus uvarum, Aspergillus nomiae, Aspergillus parasiticus, Aspergillus tamarii, Aspergillus turcosus, Aspergillus caelatus, Aspergillus pseudotamarii, Aspergillus lentulus, Aspergillus udagawae, Aspergillus viridinutans, Aspergillus pseudoviridinutans, Aspergillus fumigatiaffinis, Aspergillus ochraceoroseus, Aspergillus wentii, Aspergillus melleus, Aspergillus hiratsukae, Aspergillus felis, Aspergillus rambellii, Aspergillus arachidicola, Aspergillus thermomutatus, Aspergillusfischeri, Aspergillus terreus, Aspergillus puulaauensis, Aspergillus nidulans, Aspergillus calidoustus, and Aspergillus tanneri. Examples of the cpr gene derived from Aspergillus clavatus include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 19, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 78. Examples of the cpr gene derived from Aspergillus niger include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 31, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 82. In one or more embodiments, the genus Cochliobolus includes Cochliobolus lunatus, Cochliobolus victoriae, Cochliobolus heterostrophus, Cochliobolus carbonum, Cochliobolus sativus, Cochliobolus miyabeanus, Cochliobolus kusanoi, and Cochliobolus spicifer. Examples of the cpr gene derived from Cochliobolus lunatus include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 22 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 79. In one or more embodiments, the genus Phanerochaete includes Phanerochaete chrysosporium, Phanerochaete sordida, and Phanerochaete carnosa, etc. Examples of the cpr gene derived from Phanerochaete chrysosporium include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 25, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 80. In one or more embodiments, the genus Neurospora includes Neurospora crassa, Neurospora tetrasperm, Neurospora discreta, Neurospora intermedia, Neurospora sitophila, and Neurospora metzenbergii. Examples of the cpr gene derived from Neurospora crassa include a gene consisting of the nucleotide sequence shown in SEQ ID NO:28 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO:81. In one or more embodiments, the genus Rhodotorula includes Rhodotorula minuta, Rhodotorula gracilis, Rhodotorula rubescens, Rhodotorula creatinivora, Rhodotorula diobovata, Rhodotorula bogoriensis, and Rhodotorula mucilaginosa. Examples of the cpr gene derived from Rhodotorula minuta include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 34 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 83.

[0033] The cpr gene is not particularly limited and may be, for example, any of the following genes (A7), (A8), and (A9). (A7) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 78, 79, 80, 81, 82, or 83, or a gene encoding a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 78, 79, 80, 81, 82, or 83; (A8) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 78, 79, 80, 81, 82, or 83, and which encodes a polypeptide having a function of donating electrons to a polypeptide encoded by a cyp gene, or a gene encoding a polypeptide consisting of an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 78, 79, 80, 81, 82, or 83, and which encodes a polypeptide having a function of donating electrons to a polypeptide encoded by a cyp gene; (A9) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 78, 79, 80, 81, 82 or 83, and which encodes a polypeptide having the function of donating electrons to a polypeptide encoded by the cyp gene, or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 78, 79, 80, 81, 82 or 83, and which encodes a polypeptide having the function of donating electrons to a polypeptide encoded by the cyp gene.

[0034] The cpr gene is not particularly limited and may be, for example, any of the following genes (A10), (A11) and (A13). (A10) a gene having a nucleotide sequence shown in SEQ ID NO: 19, 22, 25, 28, 31, or 34, or a gene consisting of a nucleotide sequence shown in SEQ ID NO: 19, 22, 25, 28, 31, or 34; (A11) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 19, 22, 25, 28, 31, or 34, and encoding a polypeptide having the function of donating electrons to a polypeptide encoded by the cyp gene, or a gene consisting of a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 19, 22, 25, 28, 31, or 34, and encoding a polypeptide having the function of donating electrons to a polypeptide encoded by the cyp gene; (A12) A gene that hybridizes under stringent conditions with a gene having a base sequence complementary to a gene having a base sequence shown in SEQ ID NO: 19, 22, 25, 28, 31 or 34, and encodes a polypeptide having the function of donating electrons to a polypeptide encoded by the cyp gene, or a gene that hybridizes under stringent conditions with a gene having a base sequence complementary to a gene consisting of the base sequence shown in SEQ ID NO: 19, 22, 25, 28, 31 or 34, and encodes a polypeptide having the function of donating electrons to a polypeptide encoded by the cyp gene.

[0035] In one or more embodiments, the cpr gene is preferably a cpr gene derived from Aspergillus clavatus from the viewpoint of improving m-aminophenol productivity. From the same viewpoint, in one or more embodiments, the cpr gene is preferably a gene having the base sequence shown in SEQ ID NO: 19 or a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 78, and more preferably a gene consisting of the base sequence shown in SEQ ID NO: 19 or a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 78.

[0036] In one or more embodiments, the combination of the cyp gene and the cpr gene may be a combination of at least one of the cyp gene derived from Aspergillus clavatus, the cyp gene derived from Cochliobolus lunatus, the cyp gene derived from Phanerochaete chrysosporium, the cyp gene derived from Neurospora crassa, and the cyp gene derived from Aspergillus niger, and the cpr gene derived from Aspergillus clavatus, from the viewpoint of improving the productivity of m-aminophenol. In the same respect, the combination of the cyp gene and the cpr gene may be a combination of the cyp gene derived from Aspergillus clavatus and the cpr gene derived from Aspergillus clavatus, and a combination of the cyp gene derived from Aspergillus niger and the cpr gene derived from Aspergillus clavatus, in one or more embodiments. From a similar viewpoint, in one or more embodiments, the combination of the cyp gene and the cpr gene may be a combination of a gene having a nucleotide sequence shown in SEQ ID NO: 1, 4, 7, 10, or 13 with a gene having a nucleotide sequence shown in SEQ ID NO: 19, or a combination of a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 72, 73, 74, 75, or 76 with a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 78. From a similar viewpoint, in one or more embodiments, the combination of the cyp gene and the cpr gene may be a combination of a gene having a nucleotide sequence shown in SEQ ID NO: 1 with a gene having a nucleotide sequence shown in SEQ ID NO: 19, or a combination of a gene having a nucleotide sequence shown in SEQ ID NO: 13 with a gene having a nucleotide sequence shown in SEQ ID NO: 19. From a similar viewpoint, in one or more embodiments, the combination of the cyp gene and the cpr gene may be a combination of a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 72 with a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 78, or a combination of a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 76 with a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 78.

[0037] In one or more embodiments, whether or not a gene is "a gene encoding an enzyme having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid" can be evaluated by carrying out a reaction of producing 2-amino-4-hydroxybenzoic acid using anthranilic acid as a substrate, using a transformant prepared by introducing the gene to be evaluated into Corynebacterium glutamicum so that the gene can be expressed. When production of 2-amino-4-hydroxybenzoic acid or an increase in the amount of production is confirmed, the gene can be determined to be a gene encoding an enzyme having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid. The production of 2-amino-4-hydroxybenzoic acid can be measured based on the description in the Examples of the present specification.

[0038] [Gene (B)] In the present disclosure, the gene (B) may be one type of gene or a combination of two or more types of genes in one or more embodiments. Examples of the gene (B) encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity include, but are not limited to, genes encoding an enzyme having decarboxylation activity for 2-amino-4-hydroxybenzoic acid in one or more embodiments. Examples of the gene (B) in one or more embodiments include the decarboxylase gene ubiD and the decarboxylase gene sdc.

[0039] The ubiD gene is a gene encoding a prenylated flavinine nucleotide (prFMN)-dependent decarboxylase, and the coenzyme prFMN is synthesized by a flavin prenyltransferase encoded by the ubiX gene. Thus, the polypeptide encoded by the ubiD gene can preferably have 2-amino-4-hydroxybenzoic acid decarboxylase activity in combination with the polypeptide encoded by the ubiX gene.

[0040] The ubiD and ubiX genes may be under the control of a single promoter. It is known that the ubiH gene may exist in the same genome as the ubiD gene. In one or more embodiments, from the viewpoint of improving m-aminophenol productivity, it is preferable that the ubiX gene in the same genome as the ubiD gene is introduced into the microbial host together with the ubiD gene. In addition, when the ubiH gene is present in the same genome as the ubiD gene, it is preferable to introduce the ubiH gene together with the ubiD gene and the ubiX gene from the viewpoint of improving m-aminophenol productivity. Thus, in one or more embodiments, examples of the gene (B) include the ubiD gene, the ubiDX gene, the ubiXD gene, the ubiDH gene, the ubiHD gene, the ubiXDH gene, the ubiHDX gene, the ubiDXH gene, the ubiDHX gene, the ubiXHD gene, and the ubiHXD gene, and the like, and from the viewpoint of improving m-aminophenol productivity, the ubiXDH gene, the ubiHDX gene, the ubiDXH gene, the ubiDHX gene, the ubiXHD gene, and the ubiHXD gene are preferable, and the ubiXDH gene is more preferable. In one or more embodiments, the ubiD gene and the ubiX gene and / or the ubiH gene may be introduced in combination with the ubiD gene and the ubiX gene and / or the ubiH gene of the same genus (or species), and it is not necessary to introduce in combination with the ubiD gene and the ubiX gene and / or the ubiH gene from the same genus (or species). Even when the ubiD gene and the ubiX gene and / or the ubiH gene from any different genera (or species) are introduced in combination into the host, it goes without saying that the ubiD gene and the ubiX gene and / or the ubiH gene from any different genera (or species) still have the activity of decarboxylating 2-amino-4-hydroxybenzoic acid to produce m-aminophenol.

[0041] In one or more embodiments, the ubiD gene and the ubiX gene and / or the ubiH gene may be under the control of one promoter, or may be under the control of separate promoters. In the present disclosure, the term "ubiXHD genes" means that the ubiX gene, the ubiH gene, and the ubiD gene form an operon in this order.

[0042] [ubiD gene] The origin of the ubiD gene is not particularly limited, and examples include the genera Enterobacter, Pantoea, Escherichia, and Citrobacter. In one or more embodiments, the Enterobacter genus bacteria include Enterobacter aerogenes, Enterobacter sakazakii, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter asburiae, Enterobacter bugandensis, Enterobacter cancerogenus, Enterobacter chengduensis, Enterobacter huaxiensis, Enterobacter kobei, Enterobacter ludwigii, Enterobacter mori, Enterobacter quasiroggenkampii, Enterobacter roggenkampii, Enterobacter sichuanensis, Enterobacter soli, and Enterobacter sp. Examples of the ubiD gene derived from Enterobacter aerogenes include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 95 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 84. Examples of the ubiD gene derived from Enterobacter sakazakii include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 97, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 86. Examples of the ubiD gene derived from Enterobacter cloacae include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 98, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 87. Examples of the ubiD gene derived from Enterobacter hormaechei include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 99, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 88. In one or more embodiments, the genus Pantoea includes Pantoea ananatis, Pantoea vagans, Pantoea rwandensis, Pantoea agglomerans, Pantoea stewartii, Pantoea alhagi, Pantoea eucalypti, Pantoea dispersa, Pantoea eucrina, Pantoea jilinensis, and Pantoea anthophila. Examples of the ubiD gene derived from Pantoea ananatis include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 96 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 85. In one or more embodiments, bacteria of the genus Escherichia include Escherichia coli W, Escherichia fergusonii, Escherichia albertii, Escherichia marmotae, and Escherichia ruysiae. Examples of the ubiD gene derived from Escherichia coli W include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 100, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 89. Examples of the ubiD gene derived from Escherichia fergusonii include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 101, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 90. In one or more embodiments, the genus Citrobacter includes Citrobacter koseri, Citrobacter youngae, Citrobacter amalonaticus, Citrobacter arsenatis, Citrobacter braakii, Citrobacter farmeri, Citrobacter freundii, Citrobacter pasteurii, Citrobacter portucalensis, Citrobacter rodentium, Citrobacter sedlakii, Citrobacter sp., Citrobacter telavivensis, Citrobacter tructae, and Citrobacter werkmanii. Examples of the ubiD gene derived from Citrobacter koseri include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 102, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 91. Examples of the ubiD gene derived from Citrobacter youngae include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 103, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 92.

[0043] The ubiD gene is not particularly limited, and may be, for example, any one of the following genes (b1), (b2), and (b3). (b1) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91, or 92, or a gene encoding a polypeptide consisting of an amino acid sequence represented by SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91, or 92; (b2) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91, or 92, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; or a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91, or 92, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (b3) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91 or 92, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91 or 92, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

[0044] The ubiD gene is not particularly limited, and may be, for example, any one of the following genes (b4), (b5), and (b6). (b4) a gene having a nucleotide sequence represented by SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102, or 103, or a gene consisting of a nucleotide sequence represented by SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102, or 103; (b5) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102, or 103, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity. or a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102, or 103, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (b6) A gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having a nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102 or 103 and encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene consisting of a nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102 or 103 and encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

[0045] In one or a plurality of embodiments, the ubiD gene is preferably the ubiD gene derived from Enterobacter aerogenes, the ubiD gene derived from Pantoea ananatis, the ubiD gene derived from Enterobacter sakazakii, the ubiD gene derived from Enterobacter cloacae, the ubiD gene derived from Enterobacter hormaechei, the ubiD gene derived from Escherichia coli W, the ubiD gene derived from Escherichia fergusonii, the ubiD gene derived from Citrobacter koseri, and the ubiD gene derived from Citrobacter youngae, and more preferably the ubiD gene derived from Enterobacter aerogenes, the ubiD gene derived from Pantoea ananatis, the ubiD gene derived from Enterobacter sakazakii, the ubiD gene derived from Enterobacter cloacae, the ubiD gene derived from Enterobacter hormaechei, the ubiD gene derived from Escherichia coli W, and the ubiD gene derived from Escherichia fergusonii, and More preferred are the ubiD gene from P. aerogenes and the ubiD gene from Pantoea ananatis. From a similar standpoint, in one or more embodiments, the ubiD gene is preferably a gene having a nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102 or 103, or a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91 or 92, more preferably a gene having a nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100 or 101, or a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89 or 90, and even more preferably a gene having a nucleotide sequence shown in SEQ ID NO: 95 or 96, or a gene encoding a polypeptide having an amino acid sequence shown in SEQ ID NO: 84 or 85. From a similar standpoint, in one or more embodiments, the ubiD gene is preferably a gene consisting of the nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100, 101, 102 or 103, or a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89, 90, 91 or 92, more preferably a gene consisting of the nucleotide sequence shown in SEQ ID NO: 95, 96, 97, 98, 99, 100 or 101, or a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 84, 85, 86, 87, 88, 89 or 90, and even more preferably a gene consisting of the nucleotide sequence shown in SEQ ID NO: 95 or 96, or a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 84 or 85.

[0046] [ubiX gene] The origin of the ubiX gene is not particularly limited, and examples include the genera Enterobacter, Pantoea, Escherichia, and Citrobacter. In one or more embodiments, the Enterobacter genus bacteria include Enterobacter aerogenes, Enterobacter sakazakii, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter asburiae, Enterobacter bugandensis, Enterobacter cancerogenus, Enterobacter chengduensis, Enterobacter huaxiensis, Enterobacter kobei, Enterobacter ludwigii, Enterobacter mori, Enterobacter quasiroggenkampii, Enterobacter roggenkampii, Enterobacter sichuanensis, Enterobacter soli, and Enterobacter sp. Examples of the ubiX gene derived from Enterobacter aerogenes include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 104 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 122. Examples of Enterobacter sakazakii include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 106 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 124. Examples of Enterobacter cloacae include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 107 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 125. Examples of Enterobacter hormaechei include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 108 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 126. In one or more embodiments, the genus Pantoea includes Pantoea ananatis, Pantoea vagans, Pantoea rwandensis, Pantoea agglomerans, Pantoea stewartii, Pantoea alhagi, Pantoea eucalypti, Pantoea dispersa, Pantoea eucrina, Pantoea jilinensis, and Pantoea anthophila. Examples of the ubiX gene derived from Pantoea ananatis include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 105 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 123. In one or more embodiments, examples of Escherichia bacteria include Escherichia coli W, Escherichia fergusonii, Escherichia albertii, Escherichia marmotae, and Escherichia ruysiae. Examples of the ubiX gene derived from Escherichia coli W include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 109, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 127. Examples of the ubiX gene derived from Escherichia fergusonii include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 110, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 128. In one or more embodiments, the genus Citrobacter includes Citrobacter koseri, Citrobacter youngae, Citrobacter amalonaticus, Citrobacter arsenatis, Citrobacter braakii, Citrobacter farmeri, Citrobacter freundii, Citrobacter pasteurii, Citrobacter portucalensis, Citrobacter rodentium, Citrobacter sedlakii, Citrobacter sp., Citrobacter telavivensis, Citrobacter tructae, and Citrobacter werkmanii. Examples of the ubiX gene derived from Citrobacter koseri include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 111, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 129. Examples of the ubiX gene derived from Citrobacter youngae include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 112, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 130. The ubiX gene may form an operon with the ubiD gene and / or the ubiH gene, or may not form an operon.

[0047] The ubiX gene is not particularly limited and may be, for example, any of the following genes (b7), (b8), and (b9). (b7) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 122, 123, 124, 125, 126, 127, 128, 129, or 130, or a gene encoding a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 122, 123, 124, 125, 126, 127, 128, 129, or 130; (b8) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 122, 123, 124, 125, 126, 127, 128, 129, or 130, wherein the gene encodes a polypeptide having flavin prenyltransferase activity. or a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 122, 123, 124, 125, 126, 127, 128, 129, or 130, wherein the gene encodes a polypeptide having flavin prenyltransferase activity; (b9) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 122, 123, 124, 125, 126, 127, 128, 129, or 130, and which encodes a polypeptide having flavin prenyltransferase activity; or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 122, 123, 124, 125, 126, 127, 128, 129, or 130, and which encodes a polypeptide having flavin prenyltransferase activity. In one or more embodiments, the polypeptides encoded by the genes (b8) and (b9) may exhibit 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene.

[0048] The ubiX gene is not particularly limited and may be, for example, any of the following genes (b10), (b11) and (b12). (b10) a gene having a nucleotide sequence represented by SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, or 112, or a gene consisting of a nucleotide sequence represented by SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, or 112; (b11) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, or 112, and encoding a polypeptide having flavin prenyltransferase activity, or a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111, or 112, and encoding a polypeptide having flavin prenyltransferase activity; (b12) A gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111 or 112, and which encodes a polypeptide having flavin prenyltransferase activity, or a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene consisting of the nucleotide sequence shown in SEQ ID NO: 104, 105, 106, 107, 108, 109, 110, 111 or 112, and which encodes a polypeptide having flavin prenyltransferase activity. In one or more embodiments, the polypeptides encoded by the genes (b11) and (b12) may exhibit 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene.

[0049] [ubiH gene] The origin of the ubiH gene is not particularly limited, and examples include the genera Enterobacter, Pantoea, Escherichia, and Citrobacter. In one or more embodiments, the Enterobacter genus bacteria include Enterobacter aerogenes, Enterobacter sakazakii, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter asburiae, Enterobacter bugandensis, Enterobacter cancerogenus, Enterobacter chengduensis, Enterobacter huaxiensis, Enterobacter kobei, Enterobacter ludwigii, Enterobacter mori, Enterobacter quasiroggenkampii, Enterobacter roggenkampii, Enterobacter sichuanensis, Enterobacter soli, and Enterobacter sp. Examples of the ubiH gene derived from Enterobacter aerogenes include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 113 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 131. Examples of Enterobacter sakazakii include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 115, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 133. Examples of Enterobacter cloacae include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 116, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 134. Examples of Enterobacter hormaechei include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 117, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 135. In one or more embodiments, the genus Pantoea includes Pantoea ananatis, Pantoea vagans, Pantoea rwandensis, Pantoea agglomerans, Pantoea stewartii, Pantoea alhagi, Pantoea eucalypti, Pantoea dispersa, Pantoea eucrina, Pantoea jilinensis, and Pantoea anthophila. Examples of the ubiH gene derived from Pantoea ananatis include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 114 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 132. In one or more embodiments, bacteria of the genus Escherichia include Escherichia coli W, Escherichia fergusonii, Escherichia albertii, Escherichia marmotae, and Escherichia ruysia. Examples of the ubiH gene derived from Escherichia coli W include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 118, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 136. Examples of the ubiH gene derived from Escherichia fergusonii include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 119, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 137. In one or more embodiments, the genus Citrobacter includes Citrobacter koseri, Citrobacter youngae, Citrobacter amalonaticus, Citrobacter arsenatis, Citrobacter braakii, Citrobacter farmeri, Citrobacter freundii, Citrobacter pasteurii, Citrobacter portucalensis, Citrobacter rodentium, Citrobacter sedlakii, Citrobacter sp., Citrobacter telavivensis, Citrobacter tructae, and Citrobacter werkmanii. Examples of the ubiH gene derived from Citrobacter koseri include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 120, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 138. Examples of the ubiH gene derived from Citrobacter youngae include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 121, and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 139. The ubiH gene may form an operon with the ubiD gene and / or the ubiX gene, or may not form an operon.

[0050] The ubiH gene is not particularly limited and may be, for example, any of the following genes (b13), (b14), and (b15). (b13) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 131, 132, 133, 134, 135, 136, 137, 138, or 139, or a gene encoding a polypeptide consisting of an amino acid sequence represented by SEQ ID NO: 131, 132, 133, 134, 135, 136, 137, 138, or 139; (b14) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence represented by SEQ ID NO: 131, 132, 133, 134, 135, 136, 137, 138, or 139, wherein the gene encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene. a gene encoding a polypeptide consisting of an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 131, 132, 133, 134, 135, 136, 137, 138, or 139, which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene; (b15) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 131, 132, 133, 134, 135, 136, 137, 138 or 139, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene; or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 131, 132, 133, 134, 135, 136, 137, 138 or 139, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene.

[0051] The ubiH gene is not particularly limited and may be, for example, any of the following genes (b16), (b17), and (b18). (b16) a gene having a nucleotide sequence represented by SEQ ID NO: 113, 114, 115, 116, 117, 118, 119, 120, or 121, or a gene consisting of a nucleotide sequence represented by SEQ ID NO: 113, 114, 115, 116, 117, 118, 119, 120, or 121; (b17) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 113, 114, 115, 116, 117, 118, 119, 120, or 121, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene. a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 113, 114, 115, 116, 117, 118, 119, 120, or 121, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene; (b18) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene having a nucleotide sequence shown in SEQ ID NO: 113, 114, 115, 116, 117, 118, 119, 120 or 121, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene; or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene consisting of the nucleotide sequence shown in SEQ ID NO: 113, 114, 115, 116, 117, 118, 119, 120 or 121, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity in combination with a polypeptide encoded by the ubiD gene.

[0052] [ubiXDH gene] The origin of the ubiXDH gene is not particularly limited, and examples thereof include the genera Enterobacter, Pantoea, Escherichia, and Citrobacter. In one or more embodiments, the Enterobacter genus bacteria include Enterobacter aerogenes, Enterobacter sakazakii, Enterobacter cloacae, Enterobacter hormaechei, Enterobacter asburiae, Enterobacter bugandensis, Enterobacter cancerogenus, Enterobacter chengduensis, Enterobacter huaxiensis, Enterobacter kobei, Enterobacter ludwigii, Enterobacter mori, Enterobacter quasiroggenkampii, Enterobacter roggenkampii, Enterobacter sichuanensis, Enterobacter soli, and Enterobacter sp. An example of the ubiXDH gene derived from Enterobacter aerogenes is a gene consisting of the base sequence shown in SEQ ID NO: 37. A gene consisting of the nucleotide sequence shown in SEQ ID NO: 37 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 122, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 84, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 131. An example of the ubiXDH gene of Enterobacter sakazakii is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 43. A gene consisting of the nucleotide sequence shown in SEQ ID NO: 43 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 124, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 86, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 133. An example of the ubiXDH gene of Enterobacter cloacae is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 46.A gene consisting of the nucleotide sequence shown in SEQ ID NO: 46 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 125, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 87, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 134. An example of the ubiXDH gene of Enterobacter hormaeche is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 49. A gene consisting of the nucleotide sequence shown in SEQ ID NO: 49 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 126, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 88, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 135. In one or more embodiments, the genus Pantoea includes Pantoea ananatis, Pantoea vagans, Pantoea rwandensis, Pantoea agglomerans, Pantoea stewartii, Pantoea alhagi, Pantoea eucalypti, Pantoea dispersa, Pantoea eucrina, Pantoea jilinensis, and Pantoea anthophila. An example of the ubiXDH gene derived from Pantoea ananatis is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 40. The gene consisting of the nucleotide sequence shown in SEQ ID NO: 40 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 123, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 85, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 132. In one or more embodiments, the genus Escherichia includes Escherichia coli W, Escherichia fergusonii, Escherichia albertii, Escherichia marmotae, Escherichia ruysiae, and the like. An example of the ubiXDH gene derived from Escherichia coli W is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 52. The gene consisting of the nucleotide sequence shown in SEQ ID NO: 52 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 127, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 89, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 136. An example of the ubiXDH gene derived from Escherichia fergusonii is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 55. The gene consisting of the nucleotide sequence shown in SEQ ID NO: 55 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 128, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 90, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 137. In one or more embodiments, the genus Citrobacter may include Citrobacter koseri and Citrobacter youngae. An example of the ubiXDH gene derived from Citrobacter koseri is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 58. The gene consisting of the nucleotide sequence shown in SEQ ID NO: 58 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 129, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 91, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 138. An example of the ubiXDH gene derived from Citrobacter youngae is a gene consisting of the nucleotide sequence shown in SEQ ID NO: 61. The gene consisting of the nucleotide sequence shown in SEQ ID NO: 61 encodes a polypeptide (ubiX gene) consisting of the amino acid sequence shown in SEQ ID NO: 130, a polypeptide (ubiD gene) consisting of the amino acid sequence shown in SEQ ID NO: 92, and a polypeptide (ubiH gene) consisting of the amino acid sequence shown in SEQ ID NO: 139.

[0053] The ubiXDH gene is not particularly limited and may be, for example, any of the following genes (b19), (b20), and (b21). (b19) a gene having a nucleotide sequence represented by SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58, or 61, or a gene consisting of a nucleotide sequence represented by SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58, or 61; (b20) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58, or 61, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58, or 61, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (b21) A gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58 or 61 and encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene consisting of the nucleotide sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58 or 61 and encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

[0054] In one or more embodiments, the ubiXDH gene is preferably the ubiXDH gene derived from Enterobacter aerogenes, the ubiXDH gene derived from Pantoea ananatis, the ubiXDH gene derived from Enterobacter sakazakii, the ubiXDH gene derived from Enterobacter cloacae, the ubiXDH gene derived from Enterobacter hormaechei, the ubiXDH gene derived from Escherichia coli W, the ubiXDH gene derived from Escherichia fergusonii, the ubiXDH gene derived from Citrobacter koseri, or the ubiXDH gene derived from Citrobacter youngae, from the viewpoint of improving the productivity of m-aminophenol. More preferred are the ubiXDH genes from Enterobacter aerogenes and Pantoea ananatis. For the same reason, in one or more embodiments, the ubiXDH gene is preferably a gene having a base sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58 or 61, more preferably a gene having a base sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52 or 55, and even more preferably a gene having a base sequence shown in SEQ ID NO: 37 or 40. From a similar standpoint, in one or more embodiments, the ubiXDH gene is preferably a gene consisting of the base sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52, 55, 58 or 61, more preferably a gene consisting of the base sequence shown in SEQ ID NO: 37, 40, 43, 46, 49, 52 or 55, and even more preferably a gene consisting of the base sequence shown in SEQ ID NO: 37 or 40.

[0055] [sdc gene] The origin of the sdc gene is not particularly limited, and examples thereof include the genus Cutaneotrichosporon and the genus Aureobasidium. In one or more embodiments, the genus Cutaneotrichosporon includes Cutaneotrichosporon moniliiforme, Cutaneotrichosporon oleaginosum, Cutaneotrichosporon dermatis, Cutaneotrichosporon curvatum, Cutaneotrichosporon mucoides, Cutaneotrichosporon cutaneum, and Cutaneotrichosporon jirovecii. Examples of the sdc gene derived from Cutaneotrichosporon moniliiforme include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 64 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 93. In one or more embodiments, examples of the Aureobasidium genus include Aureobasidium pullulans, Aureobasidium pullulans var. melanigenum, Aureobasidium mansonii, Aureobasidium sp., Aureobasidium melanogenum, and Aureobasidium foliicola. Examples of the sdc gene derived from Aureobasidium pullulans include a gene consisting of the nucleotide sequence shown in SEQ ID NO: 67 and a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 94.

[0056] The sdc gene is not particularly limited and may be, for example, any of the following genes (b22), (b23), and (b24). (b22) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 93 or 94, or a gene encoding a polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 93 or 94; (b23) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 93 or 94, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene encoding a polypeptide consisting of an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 93 or 94, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (b24) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 93 or 94, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 93 or 94, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

[0057] The sdc gene is not particularly limited and may be, for example, any of the following genes (b25), (b26), and (b27). (b25) a gene having a nucleotide sequence represented by SEQ ID NO: 64 or 67, or a gene consisting of a nucleotide sequence represented by SEQ ID NO: 64 or 67; (b26) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 64 or 67, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 64 or 67, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (b27) A gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO: 64 or 67 and encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity, or a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene consisting of the nucleotide sequence shown in SEQ ID NO: 64 or 67 and encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

[0058] In one or more embodiments, whether or not the gene is a "gene encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity" can be evaluated by carrying out a decarboxylation reaction of 2-amino-4-hydroxybenzoic acid using a transformant prepared by expressibly introducing the gene to be evaluated into Corynebacterium glutamicum. When the production of m-aminophenol or an increase in the amount of production is confirmed by decarboxylating 2-amino-4-hydroxybenzoic acid, the gene can be determined to be a gene encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity. The production of m-aminophenol can be measured based on the description of the Examples in the present specification. In the present disclosure, the "gene encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity" can also be said to be a gene encoding an enzyme having an activity of producing m-aminophenol by decarboxylation of 2-amino-4-hydroxybenzoic acid.

[0059] In one embodiment, from the standpoint of improving m-aminophenol productivity, the transformant of the present disclosure is preferably a microbial host capable of producing anthranilic acid, in which the cyp gene, cpr gene, and ubiXDH gene are introduced in an expressible manner.

[0060] In one embodiment, the transformant according to the present disclosure may have enhanced production of m-aminophenol from sugar by increasing the production of anthranilic acid, which is an endogenous precursor as a reaction substrate for the introduced gene (A).

[0061] Although not essential, in one embodiment, the transformant according to the present disclosure may optionally have enhanced activity of one or more enzymes contained in at least one of the shikimic acid pathway, the sugar metabolic pathway (iolT1-ppgk), and the nonoxidative pentose phosphate pathway. The enhancement of the enzyme activity is not particularly limited, and may be achieved, for example, by enhancing the expression of the gene encoding the enzyme.

[0062] Anthranilic acid is a biosynthetic intermediate of tryptophan, an aromatic amino acid, and is produced by a catalytic reaction of anthranilic acid synthase using chorismate, which is produced in the shikimic acid pathway, a common metabolic pathway involved in aromatic amino acid production. For this reason, the metabolic flux of the shikimic acid pathway may be increased in order to produce m-aminophenol at a high level. FIG. 2 is a schematic diagram of an example of an entire sugar metabolic pathway showing the metabolic pathway of m-aminophenol using sugars as a raw material. The sugar metabolic pathway in the present disclosure refers to various in vivo reaction systems for decomposing and converting sugars such as glucose to raw materials for the biosynthesis of various compounds, and in one or more embodiments, may include the shikimic acid pathway, the sugar metabolic pathway (iolT1-ppgk), the nonoxidative pentose phosphate pathway, the TCA cycle, and the like. However, the biosynthetic pathway of m-aminophenol shown in FIG. 2 is merely an example of the sugar metabolic pathway in the present disclosure, and the present disclosure is not limited thereto.

[0063] The metabolic engineering technique for increasing the metabolic flux of the shikimic acid pathway is not particularly limited, and in one embodiment, it may be any of the following pathways (1) to (3), or a combination of two or three of pathways (1) to (3). (1) High activation of the enzyme genes that compose the shikimate pathway (aroG, aroB, aroD, aroE, aroK, aroA, and aroC, which code for 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase, 3-dehydroquinate synthase, 3-dehydroquinate dehydratase, shikimate dehydrogenase, shikimate kinase, 5-enolpyruvylshikimate-3-phosphate synthase, and chorismate synthase, respectively) by enhancing their expression or using heterologous or mutant genes. (2) High activation by enhancing the expression of the genes constituting the non-PTS sugar transport pathway, which is an alternative sugar transport and metabolic pathway different from the phosphoenolpyruvate:sugar phosphotransferase system (PTS) commonly used as a sugar transporter in wild-type strains (iolT1 and iolT2 genes encoding myo-inositol / glucose transporters, glk gene encoding glucokinase, and ppgk gene encoding polyphosphate glucokinase). (3) High activation of the genes encoding the enzymes that make up the nonoxidative pentose phosphate pathway (tkt and tal, encoding transketolase and transaldolase, respectively) by enhancing their expression. In one or more embodiments, the metabolic modification may be, but is not limited to, at least one modification of a gene constituting each pathway, or may be two, three, or four or more modifications of a gene constituting each pathway, or may be modifications of all of the genes mentioned above in each pathway.

[0064] In order to improve the productivity of m-aminophenol, the transformant according to the present disclosure may have at least one or all of the aroG gene, aroD gene, aroE gene, aroC gene, aroK gene, and aroB gene introduced into the host.

[0065] Although not an essential component, in one embodiment, the transformant according to the present disclosure may optionally have at least one or all of the functions of a gene encoding 3-dehydroshikimate dehydratase (e.g., qsuB gene), quinic acid / shikimate dehydrogenase (e.g., qsuD gene), and lactate dehydrogenase (e.g., ldhA gene) reduced or deleted. From the viewpoint of improving m-aminophenol productivity, the transformant according to the present disclosure may have a portion of the qsuB gene, qsuD gene, and ldhA gene in the host disrupted or deleted.

[0066] In addition, in one embodiment, the transformant according to the present disclosure may be modified so that each metabolic pathway is strengthened by enhancing the expression of the various metabolic pathway genes described above or by highly activating enzyme functions through the use of heterologous (mutated) genes, etc.

[0067] [Vector / plasmid] In another aspect, the present disclosure relates to a vector for introducing the above gene (A) into a microorganism.In another aspect, the present disclosure relates to a vector for introducing the above gene (B) into a microorganism. In yet another aspect, the present disclosure relates to a vector for introducing the cyp gene and the cpr gene into a microorganism.In yet another aspect, the present disclosure relates to a vector for introducing at least one selected from the group consisting of the ubiD gene, the ubiX gene, the ubiH gene, the ubiDX gene, the ubiXD gene, the ubiDH gene, the ubiHD gene, the ubiXDH gene, the ubiHDX gene, the ubiDXH gene, the ubiDHX gene, the ubiXHD gene, the ubiHXD gene, and the sdc gene into a microorganism, preferably a vector for introducing the ubiD gene, the ubiXHD gene, or the sdc gene into a microorganism. The vector according to the present disclosure is not particularly limited and may be, for example, a plasmid.

[0068] Construction of vectors for transformation The above genes can be introduced into a microbial host by amplifying the above-described genes by PCR, cloning them into an appropriate vector that can be amplified in a microbial host such as a coryneform bacterium, and incubating the microbial host in the presence of the vector. In one or more embodiments, examples of the promoter include the promoter (PgapA) of the gapA gene encoding glyceraldehyde 3-phosphate dehydrogenase (also referred to as "glyceraldehyde 3-phosphate dehydrogenase") derived from Corynebacterium glutamicum R, the promoter (Pmdh) of the mdh gene encoding malate dehydrogenase, and the promoter (PldhA) of the ldhA gene encoding lactate dehydrogenase, with PgapA being preferred.

[0069] [Creation of transformants] Transformation The transformation method can be any known method without limitation. In one or more embodiments, such known methods include the calcium chloride / rubidium chloride method, the calcium phosphate method, DEAE-dextran mediated transfection, and electroporation (electric pulse method). When the microbial host is a coryneform bacterium, the electric pulse method is preferable. The electric pulse method can be performed by known methods [e.g., Kurusu, Y. et al., Electroporation-transformation system for Coryneform bacteria by auxotrophic complementation. Agric. Biol. Chem. 54:443-447(1990)] and [Vertes AA et al., Presence of mrr- and mcr-like restriction systems in Coryneform bacteria. Res. Microbiol. 144:181-185(1993)].

[0070] Disruption or mutation of host chromosomal genes When the microbial host is a coryneform bacterium, genes encoding competing pathways for biosynthesis, inhibitors of the biosynthetic pathway, or efflux transporters may be disrupted or deleted as necessary. The function of an enzyme protein encoded by a specific gene may be improved by introducing a mutation into a chromosome. A DNA fragment in which the entire length of a target gene is deleted is prepared by linking DNA fragments before and after the target gene, and a bacterium is transformed with the DNA to cause homologous recombination on the chromosome, thereby completely deleting the target gene on the chromosome. Alternatively, a deletion-type gene modified so that a partial sequence of the target gene is deleted and a normally functioning enzyme protein is not produced is prepared, and a bacterium is transformed with DNA containing the gene to cause homologous recombination between the deletion-type gene and the gene on the chromosome, thereby replacing the target gene on the chromosome with a deletion-type or disruption-type gene. Even if an enzyme protein encoded by a deletion-type or disruption-type gene is produced, it has a three-dimensional structure different from that of a wild-type enzyme protein, and its function is reduced or lost. In addition, a mutation can be introduced into a specific position on a chromosome by causing homologous recombination between a gene fragment in which a specific mutation has been introduced and the chromosomal region. Such gene deletion or disruption by gene replacement using homologous recombination has already been established, and includes methods using plasmids containing a temperature-sensitive replication origin, plasmids capable of conjugative transfer, and methods using suicide vectors that do not have a replication origin in the host (U.S. Pat. No. 6,303,383, JP 05-007491 A). The markerless chromosomal gene introduction vector pCRA725 is a plasmid that cannot replicate in Corynebacterium glutamicum R. In the case of a single-crossover strain with a homologous region on the chromosome introduced into the plasmid pCRA725, the strain exhibits kanamycin resistance due to the expression of the kanamycin resistance gene on pCRA725 and lethality in a sucrose-containing medium due to the expression of the sacR-sacB gene of Bacillus subtilis, whereas in the case of a double-crossover strain, the strain exhibits kanamycin sensitivity due to the loss of the kanamycin resistance gene on pCRA725 and growth in a sucrose-containing medium due to the loss of the sacR-sacB gene. Thus, the markerless chromosomal gene introduction strain exhibits kanamycin sensitivity and growth in a sucrose-containing medium.

[0071] Microbial growth In one or more embodiments, the transformant according to the present disclosure is preferably cultured and grown under aerobic conditions prior to reaction in a reaction solution. In one or more embodiments, the culture conditions are a temperature of about 25° C. to 38° C. and a time of about 12 to 48 hours. In one or more embodiments, the medium used for the aerobic culture may be a natural medium or a synthetic medium containing a carbon source, a nitrogen source, inorganic salts, other nutrients, etc. In one or more embodiments, the pH of the medium is preferably about 5 to 8.

[0072] Examples of media for coryneform bacteria include A medium [Inui, M. et al., Metabolic analysis of Corynebacterium glutamicum during lactate and succinate productions under oxygen deprivation conditions. J. Mol. Microbiol. Biotechnol. 7:182-196(2004)] and BT medium [Omumasaba, CA et al., Corynebacterium glutamicum glyceraldehyde-3-phosphate dehydrogenase isoforms with opposite, ATP-dependent regulation. J. Mol. Microbiol. Biotechnol. 8:91-103(2004)]. In one or more embodiments, the medium for E. coli may be LB medium or the like.

[0073] In one or more embodiments, the carbon source may be a carbohydrate or sugar alcohol such as glucose, fructose, sucrose, mannose, maltose, mannitol, xylose, arabinose, galactose, starch, molasses, sorbitol, or glycerin; an organic acid such as acetic acid, citric acid, lactic acid, fumaric acid, maleic acid, or gluconic acid; or an alcohol such as ethanol or propanol. If desired, a hydrocarbon such as normal paraffin may also be used. The carbon source may be used alone or in combination of two or more. In one or more embodiments, the concentration of these carbon sources in the growth medium is about 0.1 (w / v%) to about 10 (w / v%).

[0074] In one or more embodiments, examples of the nitrogen source include inorganic or organic ammonium compounds such as ammonium chloride, ammonium sulfate, ammonium nitrate, and ammonium acetate, urea, aqueous ammonia, sodium nitrate, and potassium nitrate. In one or more embodiments, examples of the nitrogen source include nitrogen-containing organic compounds such as corn steep liquor, meat extract, peptone, NZ-amine, protein hydrolysates, and amino acids. The nitrogen source may be used alone or in combination of two or more. The concentration of the nitrogen source in the growth medium varies depending on the nitrogen compound used, but is about 0.1 (w / v%) to about 10 (w / v%) in one or more embodiments.

[0075] In one or more embodiments, examples of inorganic salts include potassium dihydrogen phosphate, potassium dihydrogen phosphate, magnesium sulfate, sodium chloride, ferrous nitrate, manganese sulfate, zinc sulfate, cobalt sulfate, ammonium carbonate, calcium carbonate, etc. These inorganic salts may be used alone or in combination of two or more. The concentration of inorganic salts in the growth medium varies depending on the inorganic salt used, but in one or more embodiments, it is about 0.01 (w / v%) to about 1 (w / v%).

[0076] In one or more embodiments, examples of other nutritional substances include meat extract, peptone, polypeptone, yeast extract, dry yeast, corn steep liquor, skimmed milk powder, hydrolyzed skimmed soybean with hydrochloric acid, or extracts of animals, plants, or microbial cells, or decomposition products thereof. The concentration of the nutritional substance in the medium varies depending on the nutritional substance used, but in one or more embodiments, it is about 0.1 (w / v%) to about 10 (w / v%). Vitamins may be added as necessary. In one or more embodiments, examples of vitamins include biotin, thiamine (vitamin B1), pyridoxine (vitamin B6), pantothenic acid, inositol, and nicotinic acid.

[0077] [Method of producing m-aminophenol] The present disclosure relates to a method for producing m-aminophenol. In detail, in one aspect, the method for producing m-aminophenol according to the present disclosure may be a production method including a step of culturing a transformant according to the present disclosure in a reaction solution containing sugars to produce m-aminophenol.

[0078] The reaction liquid may contain saccharides. In one or more embodiments, the reaction liquid may be water, a buffer solution, an inorganic salt medium, the above-mentioned medium, or the like, containing saccharides. In one or more embodiments, the reaction liquid may contain nutrients other than saccharides, such as vitamins, yeast extract, and dry yeast.

[0079] In one or more embodiments, the sugars include glucose, fructose, mannose, xylose, arabinose, galactose, sucrose, maltose, lactose, cellobiose, xylobiose, trehalose, mannitol, etc. In one or more embodiments, the concentration of the sugars in the reaction solution is about 0.1 (w / v%) to 20 (w / v%), and preferably 1 (w / v%) to 20 (w / v%) or 5 (w / v%) to 20 (w / v%).

[0080] In one or more embodiments, examples of the buffer solution include phosphate buffer, tris buffer, carbonate buffer, etc. In one or more embodiments, the concentration of the buffer solution is, for example, about 10 mM to about 150 mM.

[0081] In one or more embodiments, the inorganic salt medium may include a medium containing one or more inorganic salts such as potassium monophosphate, potassium diphosphate, molybdenum sulfate, sodium chloride, ferrous nitrate, manganese sulfate, zinc sulfate, cobalt sulfate, calcium carbonate, urea, ammonium sulfate, and ferrous sulfate. Among them, a medium containing urea, ammonium sulfate, potassium monophosphate, potassium diphosphate, magnesium sulfate, and ferrous sulfate is preferable. Specific examples of the inorganic salt medium include BT medium and A medium. The concentration of inorganic salts in the medium varies depending on the inorganic salt used, but in one or more embodiments, the concentration is about 0.01 (w / v%) to about 1 (w / v%).

[0082] Reaction conditions In one or more embodiments, the reaction conditions include reducing conditions and microaerobic conditions (for example, conditions under which the dissolved oxygen concentration is controlled), etc. In one or more embodiments, which are not particularly limited, when the microbial host is Corynebacterium glutamicum, the reaction is carried out under both reducing conditions and microaerobic conditions in which Corynebacterium glutamicum does not substantially grow, and therefore m-aminophenol can be produced more efficiently.

[0083] In one or more embodiments, the reaction temperature (the survival temperature of the transformant during the reaction) is about 15° C. to 50° C. Within the above temperature range, m-aminophenol can be produced efficiently. From the viewpoint of improving the productivity of m-aminophenol, the reaction temperature is 16° C. or higher, 17° C. or higher, 18° C. or higher, 19° C. or higher, or 20° C. or higher. From the same viewpoint, the reaction temperature is 49° C. or lower, 45° C. or lower, 40° C. or lower, 35° C. or lower, 34° C. or lower, or 33° C. or lower.

[0084] In one or more embodiments, the pH of the reaction solution is preferably about 6 to 8. During the reaction, it is preferable to control the pH of the reaction solution to near neutral, particularly about 7, using an aqueous ammonia solution, an aqueous sodium hydroxide solution, or the like with a pH controller (e.g., Model: DT-1023, manufactured by Able Co., Ltd.).

[0085] In one or more embodiments, the reaction time is about 1 to 7 days, and preferably about 1 to 3 days. In one or more embodiments, the culture may be any of a batch system, a fed-batch system, and a continuous system, and among these, the batch system is preferred.

[0086] In one or more embodiments, the method for producing m-aminophenol of the present disclosure may include recovering m-aminophenol from the reaction liquid (culture), and may further include purifying the recovered m-aminophenol as necessary. The method for recovering and purifying m-aminophenol from the reaction liquid (culture) is not particularly limited. In one or more embodiments, the recovery and purification can be carried out by appropriately combining well-known ion exchange resin methods, precipitation methods, crystallization methods, recrystallization methods, concentration methods, and other methods. The m-aminophenol accumulated in the culture may be used as it is without isolation.

[0087] The present disclosure further relates to one or more of the following embodiments. [1] A transformant for producing m-aminophenol, obtained by expressibly introducing the following genes (A) and (B) into a microbial host having anthranilic acid producing ability: (A) A gene encoding an enzyme that has the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid. (B) A gene encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity. [2] The transformant according to [1], wherein the gene (A) is derived from at least one selected from the group consisting of the genera Aspergillus, Cochliobolus, Phanerochaete, Neurospora, and Rhodotorula. [3] The transformant described in [1] or [2], wherein the gene (A) includes at least one gene selected from the group consisting of (A1), (A2) and (A3) below, and at least one gene selected from the group consisting of (A7), (A8) and (A9) below. (A1) a gene encoding a polypeptide having the amino acid sequence represented by SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, or SEQ ID NO: 77; (A2) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, or SEQ ID NO:77, which, in combination with a polypeptide encoded by gene (A7), (A8), or (A9), encodes a polypeptide having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid; (A3) a gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76 or SEQ ID NO: 77, and that, in combination with the polypeptide encoded by gene (A7), (A8) or (A9), encodes a polypeptide having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid; (A7) a gene encoding a polypeptide having the amino acid sequence represented by SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, or SEQ ID NO: 83; (A8) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, or SEQ ID NO: 83, and which encodes a polypeptide having the function of donating electrons to a polypeptide encoded by gene (A1), (A2), or (A3); (A9) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82 or SEQ ID NO: 83, and that encodes a polypeptide having the function of donating electrons to a polypeptide encoded by gene (A1), (A2) or (A3). [4] The transformant described in [1] or [2], wherein the gene (A) includes at least one gene selected from the group consisting of the following (A4), (A5), and (A6), and at least one gene selected from the group consisting of the following (A10), (A11), and (A12). (A4) a gene having the nucleotide sequence represented by SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 13, or SEQ ID NO: 16; (A5) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, or SEQ ID NO:16, which encodes a polypeptide having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, in combination with a polypeptide encoded by gene (A10), (A11), or (A12); (A6) a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13 or SEQ ID NO:16, and that encodes a polypeptide having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, in combination with a polypeptide encoded by the gene (A10), (A11) or (A12); (A10) a gene having the nucleotide sequence represented by SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 28, SEQ ID NO: 31, or SEQ ID NO: 34; (A11) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:31, or SEQ ID NO:34, and encoding a polypeptide having the function of donating electrons to a polypeptide encoded by gene (A4), (A5), or (A6); (A12) A gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:34, and which encodes a polypeptide having the function of donating electrons to a polypeptide encoded by gene (A4), (A5) or (A6). [5] The transformant described in any of [1] to [4], wherein the gene (B) is derived from at least one selected from the group consisting of the genera Enterobacter, Pantoea, Escherichia, Citrobacter, Cutaneotrichosporon, and Aureobasidium. [6] The transformant according to any one of [1] to [5], wherein the gene (B) is at least a gene selected from the group consisting of the following (B1), (B2) and (B3): (B1) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, or SEQ ID NO: 94; (B2) a gene encoding a polypeptide having an amino acid sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the amino acid sequence shown in SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, or SEQ ID NO: 94, wherein the gene encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (B3) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, or SEQ ID NO:94, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity. [7] The transformant according to any one of [1] to [5], wherein the gene (B) is at least a gene selected from the group consisting of the following (B4), (B5) and (B6): (B4) a gene having a nucleotide sequence represented by SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 64, or SEQ ID NO: 67; (B5) a gene having a nucleotide sequence having 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.9% or more identity to the nucleotide sequence shown in SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 64, or SEQ ID NO: 67, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (B6) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:64, or SEQ ID NO:67, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity. [8] A transformant for producing m-aminophenol, obtained by expressibly introducing into a microbial host having anthranilic acid production ability a cyp gene encoding cytochrome P450, a cpr gene encoding cytochrome P450 reductase, and an ubiD gene or an sdc gene encoding a decarboxylase. [9] the cyp gene and the cpr gene are derived from at least one selected from the group consisting of the genera Aspergillus, Cochliobolus, Phanerochaete, Neurospora, and Rhodotorula; and / or The transformant according to [8], wherein the ubiD gene or the sdc gene is derived from at least one selected from the group consisting of the genera Enterobacter, Pantoea, Escherichia, Citrobacter, Cutaneotrichosporon, and Aureobasidium.

[10] The cyp gene is selected from the group consisting of (A1), (A2), (A3), (A4), (A5) and (A6) above, and / or The cpr gene is selected from the group consisting of (A7), (A8), (A9), (A10), (A11) and (A12) above, and / or The transformant according to [8] or [9], wherein the ubiD gene and / or the sdc gene is selected from the group consisting of (B1), (B2), (B3), (B4), (B5) and (B6).

[11] The transformant according to any one of [1] to

[10] , wherein the microbial host is a coryneform bacterium.

[12] The transformant according to any one of [1] to

[11] , wherein the microbial host is Corynebacterium glutamicum.

[13] The transformant according to any one of [1] to

[12] , wherein the microbial host is Corynebacterium glutamicum R (FERM BP-18976), ATCC13032, ATCC13869, or a transformant thereof.

[14] A method for producing m-aminophenol, comprising the step of culturing the transformant according to any one of [1] to

[13] , optionally in the presence of a sugar, to produce m-aminophenol.

[0088] The present disclosure will be further described below using examples, but the present disclosure is not limited to the following examples. EXAMPLES

[0089] [Example 1: Construction of m-aminophenol producing strain] (1) Preparation and acquisition of chromosomal DNA Aspergillus clavatus JCM 1718, Aspergillus niger JCM 22282, Citrobacter youngae ATCC 29220, Cutaneotrichosporon moniliiforme NBRC 1527, Corynebacterium glutamicum R (FERM BP-18976), Enterobacter aerogenes NBRC 13534, Enterobacter cloacae NBRC 13535, Enterobacter hormaechei ATCC 49162, Escherichia coli W NBRC 13500, Escherichia fergusonii NBRC 102419, Neurospora crassa ATCC 36373, Pantoea ananatis LMG After culturing the chromosomal DNA of 20103 according to the information provided by the strain obtaining institution, the chromosomal DNA of The chromosomal DNA of Citrobacter koseri ATCC BAA-895D-5 and Enterobacter sakazakii ATCC BAA-894D-5 was obtained from ATCC. The hydroxylase genes of Cochliobolus lunatus, Phanerodontia chrysosporium, and Cystobasidium minutum, and the decarboxylase gene of Aureobasidium pullulans were artificially synthesized with codon optimization for expression in Corynebacterium glutamicum.

[0090] (2) Construction of m-aminophenol production-related gene expression plasmid The primer sequences used to isolate the target enzyme genes are shown in Table 1. PCR was performed using a VeritiPro thermal cycler (Thermo Fisher Scientific Co., Ltd.) and PrimeSTAR HS DNA Polymerase (Takara Bio Inc.) as a reaction reagent. [Table 1]

[0091] The PCR-amplified DNA fragment was introduced into the cloning vector pCRB209 [International Publication WO2012 / 033112] containing the PgapA promoter. For the cpr gene, the PgapA promoter fusion gene fragment was introduced into the plasmid pCRB1 [NCBI GenBank: AB444682] that can coexist in Corynebacterium glutamicum. The introduced cloning vector and the obtained plasmid name are shown in Table 2. [Table 2]

[0092] (3) Construction of a plasmid for introducing m-aminophenol production-related genes into chromosome The DNA region required for markerless introduction of m-aminophenol production-related genes into the chromosome of Corynebacterium glutamicum R strain was determined based on a sequence reported to be non-essential for growth of Corynebacterium glutamicum R strain [Appl. Environ. Microbiol. 71:3369-3372 (2005)] (SSI region). This DNA region was amplified by PCR, and the resulting DNA fragment was introduced into the markerless gene introduction plasmid pCRA725 [J. Mol. Microbiol. Biotechnol. 8:243-254 (2004), JP 2007-295809 A]. The primer sequences and the resulting plasmids are shown in Table 3. [Table 3] The PgapA promoter fusion gene fragment was obtained from the m-aminophenol production-related gene expression plasmid constructed in Table 2 and introduced into the above-mentioned plasmid for chromosomal introduction. The obtained plasmid is shown in Table 4. [Table 4]

[0093] (4) Construction of a strain with m-aminophenol production-related genes introduced into the chromosome The markerless chromosomal gene introduction vector pCRA725 is a plasmid that cannot replicate in Corynebacterium glutamicum R. In the case of a single-crossover strain with a homologous region on the chromosome introduced into the plasmid pCRA725, the strain exhibits kanamycin resistance due to the expression of the kanamycin resistance gene on pCRA725 and lethality in a sucrose-containing medium due to the expression of the sacR-sacB gene derived from Bacillus subtilis, whereas in the case of a double-crossover strain, the strain exhibits kanamycin sensitivity due to the loss of the kanamycin resistance gene on pCRA725 and growth in a sucrose-containing medium due to the loss of the sacR-sacB gene. Thus, the markerless chromosomal gene introduction strain exhibits kanamycin sensitivity and growth in a sucrose-containing medium. The recombinant strain Rmap1 was constructed using the above-mentioned plasmid for chromosomal introduction of m-aminophenol production-related genes by the above-mentioned method. The host strain used was the Corynebacterium glutamicum R ldhA-disrupted strain CRZ1 [Biotechnol Bioeng. Nov;110(11):2938-2948 (2013)]. In addition, the following plasmids were used: pCRB284 [WO2017 / 169399] for aroG gene chromosome introduction, pCRB291 [WO2017 / 169399] for aroD gene chromosome introduction, pCRB293 [WO2017 / 169399] for aroE gene chromosome introduction, pCRB286 [WO2017 / 169399] for aroCKB gene chromosome introduction, pCRG65 for trpEG gene chromosome introduction, Pmdts12 for ubiXDH gene chromosome introduction, pCRB229 [WO2017 / 169399] for qsuB gene disruption, and pCRB299 [WO2017 / 169399] for qsuD gene disruption. The outline of the chromosomal gene recombination is summarized in Table 5. [Table 5]

[0094] (5) Construction of a strain carrying an expression plasmid for m-aminophenol production The above-mentioned m-aminophenol production-related gene expression plasmid was introduced into Corynebacterium glutamicum R strain or Rmap1 strain. The overview of the introduced strains is summarized in Table 6. [Table 6]

[0095] [Experiment (1)] Hydroxylase screening experiment (an experiment to hydroxylate anthranilic acid to produce 2-amino-4-hydroxybenzoic acid) The hydroxylase gene-introduced strains (MSSK01-MSSK06) constructed in Example 1 were used to examine the ability of each strain to produce 2-amino-4-hydroxybenzoic acid from anthranilic acid. Each strain was cultured in 10 ml of ACK-Glc liquid medium (A liquid medium (NH 2 ) 2 CO 2g, (NH 4 ) 2 SO 4 7g, KH 2 PO 4 0.5g, K 2 HPO 4 0.5g MgSO 4 7H 2 0.5g O, 0.6% (w / v) FeSO 4 7H 2 O and 0.42% (w / v) MnSO 4 H 2The bacteria were precultured overnight in a liquid medium (in a test tube) containing 1 ml of a mixture of 1 ml of O, 1 ml of 0.02% (w / v) biotin solution, 1 ml of 0.02% (w / v) thiamin solution, 2 g of yeast extract, and 7 g of vitamin assay casamino acid dissolved in 1 L of distilled water, supplemented with 4% glucose, 5 μg / ml of chloramphenicol, and 50 μg / ml of kanamycin. After that, the bacteria were inoculated into 10 ml of fresh ACK-Glc liquid medium containing 10 mM anthranilic acid so that the initial OD was 0.5, and the reaction was carried out at 33°C for 24 hours with shaking. The detection area of ​​2-amino-4-hydroxybenzoic acid contained in the reaction supernatant of each strain was measured by Q-TOF / MS analysis. As a result, each strain (MSSK01-MSSK06) was able to produce 2-amino-4-hydroxybenzoic acid from anthranilic acid. As shown in Table 7, the production concentrations of 2-amino-4-hydroxybenzoic acid of MSSK01, MSSK02, MSSK03, MSSK04 and MSSK05 were high, and the production concentration of 2-amino-4-hydroxybenzoic acid of MSSK01 was particularly high. [Table 7]

[0096] [Experiment (2)] Decarboxylase screening experiment (an experiment to produce m-aminophenol (MAP) by decarboxylating 2-amino-4-hydroxybenzoic acid) Using the decarboxylase gene-introduced strains (MDTS01-MDTS11) constructed in Example 1, the ability of each strain to produce m-aminophenol from 2-amino-4-hydroxybenzoic acid was examined. Each strain was cultured in 10 ml of AK-Glc liquid medium (A liquid medium (NH 2 ) 2 CO 2g, (NH 4 ) 2 SO 4 7g, KH 2 PO 4 0.5g, K 2 HPO 4 0.5g MgSO4 7H 2 0.5g O, 0.6% (w / v) FeSO 4 7H 2 O and 0.42% (w / v) MnSO 4 H 2 The bacteria were precultured overnight in a liquid medium (in a test tube) containing 1 ml of a mixture of 0 and O, 1 ml of 0.02% (w / v) biotin solution, 1 ml of 0.02% (w / v) thiamin solution, 2 g of yeast extract, and 7 g of vitamin assay casamino acid dissolved in 1 L of distilled water, to which 2% glucose and 50 μg / ml kanamycin were added. After that, the bacteria were inoculated into 10 ml of fresh AK-Glc liquid medium so that the initial OD was 0.5, and cultured with shaking at 33°C for 4 hours. The bacteria were harvested by centrifugation, and each strain was suspended in 4 mL of reaction solution (10 mM 2-amino-4-hydroxybenzoic acid, 100 mM 2-Morpholinoethanesulfonic acid, pH 5.5) to an OD of 5. The reaction was carried out at 33° C. for 1 hour with shaking. The detection area of ​​m-aminophenol contained in the reaction supernatant of each strain was measured by HPLC analysis. As a result, each strain (MDTS01-MDTS11) was able to produce m-aminophenol from 2-amino-4-hydroxybenzoic acid. As shown in Table 8, the m-aminophenol production rates of MDTS01, MDTS02, MDTS03, MDTS04, MDTS05, MDTS06 and MDTS07 were fast, and the m-aminophenol production rates of MDTS01 and MDTS02 were extremely fast. [Table 8]

[0097] [Experiment (3)] m-Aminophenol production from sugars The strains (MAIT01 and MAIT02) into which the hydroxylase gene and decarboxylase gene were introduced, constructed in Example 1, were used to examine the ability of each strain to produce m-aminophenol from sugar. Each strain was cultured in 10 ml of ACK-Glc liquid medium (A liquid medium (NH 2 ) 2 2g CO, (NH4) 2 SO 4 7g, KH 2 PO 4 0.5g, K 2 HPO 4 0.5g MgSO 4 7H 2 0.5g O, 0.6% (w / v) FeSO 4 7H 2 O and 0.42% (w / v) MnSO 4 H 2 The bacteria were precultured overnight in a liquid medium (in a test tube) containing 1 ml of a mixture of 1 ml of 0.02% (w / v) biotin solution, 1 ml of 0.02% (w / v) thiamin solution, 2 g of yeast extract, and 7 g of vitamin assay casamino acid dissolved in 1 L of distilled water, supplemented with 4% glucose, 5 μg / ml of chloramphenicol, and 50 μg / ml of kanamycin. The bacteria were then inoculated into 100 ml of fresh ACK-Glc liquid medium supplemented with 8% glucose so that the initial OD610 was 0.5, and incubated at 28°C, pH 7.0 (5N NH 3 The culture was carried out in a 200 ml jar fermenter for 24 hours under the conditions of pH > 10 (automatically adjusted by adding 0.1% DO (automatically controlled by controlling the agitation speed of 100-1500 rpm) and 0.4 vvm (40 ml air / min). After 24 hours of culture, the temperature was changed to 20°C and culture was continued for another 48 hours. After 72 hours of cultivation, the detection area of ​​m-aminophenol contained in the culture supernatant of each strain was measured by Q-TOF / MS analysis. As a result, each strain (MAIT01 and MAIT02) produced m-aminophenol from sugar (glucose). In particular, the production concentration of m-aminophenol (MAP) of MAIT01 was high, at 3.06 μM.

[0098] The abbreviated compound names and their CAS numbers shown in Figure 2 (an overall metabolic pathway diagram for explaining the biosynthetic pathway of m-aminophenol) are shown below. It goes without saying that the "compound names" shown below are only examples, and that there may be synonymous aliases. It also goes without saying that the "CAS numbers" shown below are not necessarily all-encompassing. [Table 9]

[0099] The enzymes encoded by the genes shown in Figure 2 (an overall metabolic pathway diagram for explaining the biosynthetic pathway of m-aminophenol) and their EC numbers are shown below. The "enzyme names" shown below are only examples, and it goes without saying that there may be synonymous alternative names. Furthermore, the "enzymes" encoded by the "genes" shown below are only examples, and it goes without saying that there may be "genes" that encode "enzymes" with multiple functions. [Table 10]

Claims

1. A transformant for producing m-aminophenol, which is obtained by expressibly introducing the following genes (A) and (B) into a microbial host having an anthranilic acid producing ability: (A) A gene encoding an enzyme having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid. (B) A gene encoding an enzyme having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

2. 2. The transformant according to claim 1, wherein the gene (A) is derived from at least one selected from the group consisting of the genera Aspergillus, Cochliobolus, Phanerochaete, Neurospora, and Rhodotorula.

3. The transformant described in claim 1, wherein the gene (A) includes at least one gene selected from the group consisting of the following (A1), (A2), and (A3), and at least one gene selected from the group consisting of the following (A7), (A8), and (A9). (A1) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, or SEQ ID NO: 77; (A2) a gene encoding a polypeptide having an amino acid sequence having 90% or more identity to the amino acid sequence shown in SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76 or SEQ ID NO:77, which, in combination with a polypeptide encoded by gene (A7), (A8) or (A9), encodes a polypeptide having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid; (A3) a gene that hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence represented by SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76 or SEQ ID NO:77, and that, in combination with the polypeptide encoded by gene (A7), (A8) or (A9), encodes a polypeptide having the activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid; (A7) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, or SEQ ID NO: 83; (A8) a gene encoding a polypeptide having an amino acid sequence having 90% or more identity to the amino acid sequence shown in SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, or SEQ ID NO:83, and having the function of donating electrons to the polypeptide encoded by gene (A1), (A2), or (A3); (A9) A gene that hybridizes under stringent conditions to a gene having a base sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82 or SEQ ID NO:83, and which encodes a polypeptide having the function of donating electrons to a polypeptide encoded by gene (A1), (A2) or (A3).

4. The transformant according to claim 1, wherein the gene (A) comprises at least one gene selected from the group consisting of the following (A4), (A5), and (A6), and at least one gene selected from the group consisting of the following (A10), (A11), and (A12). (A4) a gene having a nucleotide sequence represented by SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 13, or SEQ ID NO: 16; (A5) a gene having a nucleotide sequence having 90% or more identity to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13 or SEQ ID NO:16, which encodes a polypeptide having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, in combination with a polypeptide encoded by gene (A10), (A11) or (A12); (A6) A gene which hybridizes under stringent conditions with a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13 or SEQ ID NO:16, and which encodes a polypeptide having an activity of hydroxylating anthranilic acid to produce 2-amino-4-hydroxybenzoic acid, in combination with a polypeptide encoded by the gene (A10), (A11) or (A12); (A10) a gene having a nucleotide sequence represented by SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 28, SEQ ID NO: 31, or SEQ ID NO: 34; (A11) a gene having a nucleotide sequence having 90% or more identity to a gene having the nucleotide sequence shown in SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:34, which encodes a polypeptide having a function of donating electrons to a polypeptide encoded by gene (A4), (A5) or (A6); (A12) A gene that hybridizes under stringent conditions with a gene having a base sequence complementary to a gene having the base sequence shown in SEQ ID NO:19, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:34, and which encodes a polypeptide having the function of donating electrons to a polypeptide encoded by gene (A4), (A5) or (A6).

5. The transformant according to claim 1 , wherein the gene (B) is derived from at least one selected from the group consisting of the genera Enterobacter, Pantoea, Escherichia, Citrobacter, Cutaneotrichosporon, and Aureobasidium.

6. The transformant according to claim 1 , wherein the gene (B) is at least a gene selected from the group consisting of the following (B1), (B2) and (B3): (B1) a gene encoding a polypeptide having an amino acid sequence represented by SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, or SEQ ID NO: 94; (B2) a gene encoding a polypeptide having an amino acid sequence having 90% or more identity to the amino acid sequence represented by SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, or SEQ ID NO:94, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (B3) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene encoding a polypeptide having the amino acid sequence shown in SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, or SEQ ID NO:94, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

7. The transformant according to claim 1 , wherein the gene (B) is at least a gene selected from the group consisting of the following genes (B4), (B5) and (B6): (B4) a gene having a nucleotide sequence represented by SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 64, or SEQ ID NO: 67; (B5) a gene having a nucleotide sequence having 90% or more identity to the nucleotide sequence represented by SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:64, or SEQ ID NO:67, and encoding a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity; (B6) A gene that hybridizes under stringent conditions to a gene having a nucleotide sequence complementary to a gene having the nucleotide sequence shown in SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:64, or SEQ ID NO:67, and which encodes a polypeptide having 2-amino-4-hydroxybenzoic acid decarboxylation activity.

8. A microbial host capable of producing anthranilic acid, The cyp gene encoding cytochrome P450; The cpr gene encoding cytochrome P450 reductase; The ubiD gene or the sdc gene encoding a decarboxylase, A transformant for producing m-aminophenol obtained by expressibly introducing the gene.

9. A method for producing m-aminophenol, comprising a step of culturing the transformant according to any one of claims 1 to 8 to produce m-aminophenol.

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