[1] Walsh CT, Tang Y. Natural Product Biosynthesis: Chemical Logic and Enzymatic
Machinery. Royal Society of Chemistry. 2017.
[2] Devi R, Kaur T, Guleria G, Rana KL, Kour D, Yadav N, Yadav AN, Saxenac AK. New and
Future Developments in Microbial Biotechnology and Bioengineering. Chapter 9 Fungal secondary metabolites and their biotechnological applications for human health.
Elsevier. 2020, 147-161
[3] Martin JF, Liras P. ORGANIZATION AND EXPRESSION OF GENES INVOLVED IN
THE
BIOSYNTHESIS
OF
ANTIBIOTICS
AND
OTHER
SECONDARY
METABOLITES. Annual Review of Microbiology. 1989, 43, 173-206
[4] Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, Weber
T, Takano E, Breitling R. antiSMASH: rapid identification, annotation and analysis of
secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences.
Nucleic Acids Res. 2011, 39.
[5] Khaldi N, Seifuddin FT, Turner G, Haft D, Nierman WC, Wolfe KH, Fedorova ND.
SMURF: Genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol.
2010, 47, 736-741.
[6] Przystałowska H, Zeyland J, Szymanowska-Powałowska D, Szalata M, Słomski R, Lipiński
D. 1,3-Propanediol production by new recombinant Escherichia coli containing genes
from pathogenic bacteria. Microbiol Res. 2015,171, 1-7.
[7] Yang B, Liang S, Liu H, Liu J, Cui Z, Wen J. Metabolic engineering of Escherichia coli for
1,3-propanediol biosynthesis from glycerol. Bioresour Technol. 2018, 267, 599-607.
[8] Klayman DL. Qinghaosu (artemisinin): An antimalarial drug from China. Science. 1985,
228, 1049-1055.
[9] White NJ. Qinghaosu (artemisinin): the price of success. Science. 2008, 320, 330-334.
[10]
Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, et al. Production of the
antimalarial drug precursor artemisinic acid in engineered yeast. Nature. 2006, 440,
940-943.
110
[11]
C J Paddon, P J Westfall, D J Pitera, K Benjamin, K Fisher, et al. High-level semi-
synthetic production of the potent antimalarial artemisinin. Nature. 2013, 496, 528-532.
[12]
Machida M, Asai K, Sano M, Tanaka T, et al. Genome sequencing and analysis of
Aspergillus oryzae. Nature. 2005, 438, 1157-1161.
[13]
Takahashi T, Masuda T, Koyama Y. Enhanced gene targeting frequency in ku70 and
ku80 disruption mutants of Aspergillus sojae and Aspergillus oryzae. Mol Genet
Genomics. 2006, 275, 460-470.
[14]
Fujii T, Yamaoka H, Gomi K, Kitamoto K, Kumagai C. Cloning and nucleotide
sequence of the ribonuclease T1 gene (rntA) from Aspergillus oryzae and its expression
in Saccharomyces cerevisiae and Aspergillus oryzae. Biosci Biotechnol Biochem. 1995, 59,
1869-1874.
[15]
Kubodera T, Yamashita N, Nishimura A. Transformation of Aspergillus sp. and
Trichoderma reesei using the pyrithiamine resistance gene (ptrA) of Aspergillus oryzae.
Biosci Biotechnol Biochem. 2002, 66, 404-406.
[16]
Awakawa T, Yokota K, Funa N, et al. Physically discrete beta-lactamase-type
thioesterase catalyzes product release in atrochrysone synthesis by iterative type I
polyketide synthase. Chem Biol. 2009, 16, 613-623.
[17] Fujii R, Minami A, Tsukagoshi T, et al. Total biosynthesis of diterpene aphidicolin, a
specific inhibitor of DNA polymerase : heterologous expression of four biosynthetic
genes in Aspergillus oryzae. Biosci Biotechnol Biochem. 2011, 75, 1813-1817.
[18] Tagami K, Liu C, Minami A, et al. Reconstitution of biosynthetic machinery for indolediterpene paxilline in Aspergillus oryzae. J Am Chem Soc. 2013, 135, 1260-1263.
[19] Wasil Z, Pahirulzaman KA, Buttsa C, et al. One pathway, many compounds: heterologous
expression of a fungal biosynthetic pathway reveals its intrinsic potential for diversity.
Chem Sci. 2013, 4, 3845-3856.
[20] Yoshimi A, Yamaguchi S, Fujioka T, et al. Heterologous Production of a Novel Cyclic
Peptide Compound, KK-1, in Aspergillus oryzae. Front Microbiol. 2018, 9, 690.
[21] Nakajima K, Asakura T, Maruyama J, et al. Extracellular production of neoculin, a sweettasting heterodimeric protein with taste-modifying activity, by Aspergillus oryzae. Appl
111
Environ Microbiol. 2006, 72, 3716-3723.
[22] Yoon J, Maruyama J, Kitamoto K. Disruption of ten protease genes in the filamentous
fungus Aspergillus oryzae highly improves production of heterologous proteins. Appl
Microbiol Biotechnol. 2011, 89, 747-759.
[23] Hertweck C. The biosynthetic logic of polyketide diversity. Angew Chem Int Ed Engl.
2009, 48, 4688-4716.
[24] Burr DA, Chen XB, Vederas JC. Syntheses of conjugated pyrones for the enzymatic assay
of lovastatin nonaketide synthase, an iterative polyketide synthase. Org Lett. 2007, 9,
161-164.
[25] Waite M, Wakil SJ. Studies on the mechanism of fatty acid synthesis. XII. Acetyl
coenzyme A carboxylase. J Biol Chem. 1962, 237, 2750-2757.
[26] Miyahisa I, Kaneko M, Funa N, et al. Efficient production of (2S)-flavanones by
Escherichia coli containing an artificial biosynthetic gene cluster. Appl Microbiol
Biotechnol. 2005, 68, 498-504.
[27] Buu LM, Chen YC, Lee FJ. Functional characterization and localization of acetyl-CoA
hydrolase, Ach1p, in Saccharomyces cerevisiae. J Biol Chem. 2003, 278, 17203-17209.
[28] Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular
energy. Nat Rev Mol Cell Biol. 2007, 8, 774-785.
[29] Jiang R, Carlson M. The Snf1 protein kinase and its activating subunit, Snf4, interact
with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex. Mol
Cell Biol. 1997, 17, 2099–2106.
[30] Zhang M, Galdieri L, Vancura A. The yeast AMPK homolog SNF1 regulates acetyl
coenzyme A homeostasis and histone acetylation. Mol Cell Biol. 2013, 33, 4701-4717.
[31] Woods A, Munday MR, Scott J, et al. Yeast SNF1 is functionally related to mammalian
AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem.
1994, 269, 19509-19515.
[32] Tamano K, Bruno KS, Koike H, et al. Increased production of free fatty acids in
Aspergillus oryzae by disruption of a predicted acyl-CoA synthetase gene. Appl Microbiol
Biotechnol. 2015, 99, 3103-3113.
112
[33] Nikawa J, Tanabe T, Ogiwara H, et al. Inhibitory effects of long-chain acyl coenzyme A
analogues on rat liver acetyl coenzyme A carboxylase. FEBS Lett. 1979, 102, 223-226.
[34] Parks LW, Casey WM. Physiological implications of sterol biosynthesis in yeast. Annu
Rev Microbiol. 1995, 49, 95-116.
[35] Magnuson K, Jackowski S, Rock CO, et al. Regulation of fatty acid biosynthesis in
Escherichia coli. Microbiol Rev. 1993, 57, 522-542.
[36] El-Sayed M, Verpoorte R. Catharanthus terpenoid indole alkaloids: biosynthesis and
regulation. Phytochem Rev. 2007, 6, 277-305.
[37] Nemec T, Jernejc K, Cimerman A. Sterols and fatty acids of different Aspergillus species.
FEMS Microbiol Lett. 1997, 149, 201-205.
[38] Alcazar-Fuoli L, Mellado E, Garcia-Effron G, et al. Ergosterol biosynthesis pathway in
Aspergillus fumigatus. Steroids. 2008, 73, 339-347.
[39] Krivoruchko A, Nielsen J. Production of natural products through metabolic engineering
of Saccharomyces cerevisiae. Curr Opin Biotechnol. 2015, 35, 7-15.
[40] Espenshade PJ, Hughes AL. Regulation of sterol synthesis in eukaryotes. Annu Rev
Genet. 2007, 41, 401-427.
[41] Itoh H, Miura A, Matsui M, et al. Knockout of the SREBP system increases production
of the polyketide FR901512 in filamentous fungal sp. No. 14919 and lovastatin in
Aspergillus terreus ATCC20542. Appl Microbiol Biotechnol. 2018, 102, 1393-1405.
[42] Basnet P, Skalko-Basnet N. Curcumin: an anti-inflammatory molecule from a curry spice
on the path to cancer treatment. Molecules. 2011, 16, 4567-4598.
[43] Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005,
41, 1955-1968.
[44] Katsuyama Y, Matsuzawa M, Funa N, et al. Production of curcuminoids by Escherichia
coli carrying an artificial biosynthesis pathway. Microbiology. 2008, 154, 2620-2628.
[45] Hwang EI, Kaneko M, Ohnishi Y, et al. Production of plant-specific flavanones by
Escherichia coli containing an artificial gene cluster. Appl Environ Microbiol. 2003, 69,
2699-2706.
[46] Yazaki K, Ogawa A, Tabata M. Isolation and characterization of two cDNAs encoding 4-
113
coumarate: CoA ligase in Lithospermum cell cultures. Plant Cell Physiol. 1995, 36, 13191329.
[47] Katsuyama Y, Matsuzawa M, Funa N, et al. In vitro synthesis of curcuminoids by type III
polyketide synthase from Oryza sativa. J Biol Chem. 2007, 282, 37702-37709.
[48] Huang Q, Lu G, Shen HM, et al. Anti-cancer properties of anthraquinones from rhubarb.
Med Res Rev. 2007, 27, 609-630.
[49] Terabayashi Y, Sano M, Yamane N, et al. Identification and characterization of genes
responsible for biosynthesis of kojic acid, an industrially important compound from
Aspergillus oryzae. Fungal Genet Biol. 2010, 47, 953-961.
[50] Tokuoka M, Seshime Y, Fujii I, et al. Identification of a novel polyketide synthasenonribosomal peptide synthetase (PKS-NRPS) gene required for the biosynthesis of
cyclopiazonic acid in Aspergillus oryzae. Fungal Genet Biol. 2008, 45, 1608-1615.
[51] Pfefferle W, Anke H, Bross M, et al. Asperfuran, a novel antifungal metabolite from
Aspergillus oryzae. J Antibiot. 1990, 43, 648-654.
[52] Yamada T, Hiratake J, Aikawa M, et al. Cysteine protease inhibitors produced by the
industrial koji mold, Aspergillus oryzae O-1018. Biosci Biotechnol Biochem. 1998, 62,
907-914.
[53] Nielsen ML, Nielsen JB, Rank C, et al. A genome-wide polyketide synthase deletion
library uncovers novel genetic links to polyketides and meroterpenoids in Aspergillus
nidulans. FEMS Microbiol Lett. 2011, 321, 157-166.
[54] Hasan H, Abd Rahim MH, Campbell L, et al. Improved lovastatin production by
inhibiting (+)-geodin biosynthesis in Aspergillus terreus. N Biotechnol. 2019, 52, 19-24.
[55] Barrios-González J, Baños JG, Covarrubias AA, Garay-Arroyo A. Lovastatin biosynthetic
genes of Aspergillus terreus are expressed differentially in solid-state and in liquid
submerged fermentation. Appl Microbiol Biotechnol. 2008, 79, 179-186.
[56] Maeda H, Sano M, Maruyama Y, et al. Transcriptional analysis of genes for energy
catabolism and hydrolytic enzymes in the filamentous fungus Aspergillus oryzae using
cDNA microarrays and expressed sequence tags. Appl Microbiol Biotechnol. 2004, 65,
74-83.
114
[57] Sanchez JF, Somoza AD, Keller NP, Wang CC. Advances in Aspergillus secondary
metabolite research in the post-genomic era. Nat Prod Rep. 2012, 29, 351-371.
[58] Tamano K, Kuninaga M, Kojima N, et al. Use of the kojA promoter, involved in kojic acid
biosynthesis, for polyketide production in Aspergillus oryzae: implications for long-term
production. BMC Biotechnol. 2019, 19, 70.
[59] Nakazawa T, Ishiuchi K, Praseuth A, et al. Overexpressing transcriptional regulator in
Aspergillus oryzae activates a silent biosynthetic pathway to produce a novel polyketide.
Chembiochem. 2012, 13, 855-861.
[60] Seshime Y, Juvvadi PR, Kitamoto K, Ebizuka Y, Fujii I. Identification of csypyrone B1 as
the novel product of Aspergillus oryzae type III polyketide synthase CsyB. Bioorg Med
Chem. 2010, 18, 4542-4546.
[61] Takahashi T, Jin FJ, Sunagawa M, et al. Generation of large chromosomal deletions in
koji molds Aspergillus oryzae and Aspergillus sojae via a loop-out recombination. Appl
Environ Microbiol. 2008, 74, 7684-7693.
[62] Takahashi T, Ogawa M, Koyama Y. Analysis of the functions of recombination-related
genes in the generation of large chromosomal deletions by loop-out recombination in
Aspergillus oryzae. Eukaryot Cell. 2012, 11, 507-517
[63] Wang B, Guo G, Wang C, et al. Survey of the transcriptome of Aspergillus oryzae via
massively parallel mRNA sequencing. Nucleic Acids Res. 2010, 38, 5075-5087.
[64] Butchko RA, Brown DW, Busman M, et al. Lae1 regulates expression of multiple
secondary metabolite gene clusters in Fusarium verticillioides. Fungal Genet Biol. 2012,
49, 602-612.
[65] Baba S, Kinoshita H, Nihira T. Identification and characterization of Penicillium
citrinum VeA and LaeA as global regulators for ML-236B production. Curr Genet. 2012,
58, 1-11.
[66] Seiboth B, Karimi RA, Phatale PA, et al. The putative protein methyltransferase LAE1
controls cellulase gene expression in Trichoderma reesei. Mol Microbiol. 2012, 84, 11501164.
[67] Nützmann HW, Fischer J, Scherlach K, et al. Distinct amino acids of histone H3 control
115
secondary metabolism in Aspergillus nidulans. Appl Environ Microbiol. 2013, 79, 6102–
6109.
[68] Shwab EK, Bok JW, Tribus M, et al. Histone deacetylase activity regulates chemical
diversity in Aspergillus. Eukaryot Cell. 2007, 6, 1656-1664.
[69] Henke MT, Soukup AA, Goering AW, et al. New Aspercryptins, Lipopeptide Natural
Products, Revealed by HDAC Inhibition in Aspergillus nidulans. ACS Chem Biol. 2016,
19, 11, 2117-2123.
[70] Fisch KM, Gillaspy AF, Gipson M, et al. Chemical induction of silent biosynthetic
pathway transcription in Aspergillus niger. J Ind Microbiol Biotechnol. 2009, 36, 11991213.
[71] Asai T, Yamamoto T, Oshima Y. Aromatic polyketide production in Cordyceps indigotica,
an entomopathogenic fungus, induced by exposure to a histone deacetylase inhibitor.
Org Lett. 2012, 14, 2006-2009.
[72] Asai T, Morita S, Taniguchi T, et al. Epigenetic stimulation of polyketide production in
Chaetomium cancroideum by an NAD(+)-dependent HDAC inhibitor. Org Biomol
Chem. 2016 14, 646-651.
[73] Ogawa M, Tokuoka M, Jin FJ, et al. Genetic analysis of conidiation regulatory pathways
in koji-mold Aspergillus oryzae. Fungal Genet Biol. 2010, 47, 10-18.
[74] Oakley BR, Rinehart JE, Mitchell BL, et al. Cloning, mapping and molecular analysis of
the pyrG (orotidine-5'-phosphate decarboxylase) gene of Aspergillus nidulans. Gene.
1987, 61, 385-399.
[75] Tamano K, Bruno KS, Karagiosis SA, et al. Increased production of fatty acids and
triglycerides in Aspergillus oryzae by enhancing expressions of fatty acid synthesisrelated genes. Appl Microbiol Biotechnol. 2013, 97, 269-281.
[76] Gilbert IH, Ginty M, O'Neill JA, et al. Synthesis of β-keto and α, β-unsaturated Nacetylcysteamine thioesters. Bioorg Med Chem Lett. 1995, 5, 1587-1590.
[77] Kitamoto N, Matsui J, Kawai Y, et al. Utilization of the TEF1-alpha gene (TEF1)
promoter for expression of polygalacturonase genes, pgaA and pgaB, in Aspergillus
oryzae. Appl Microbiol Biotechnol. 1998, 50, 85-92.
116
[78] Kitamoto N, Yoshino-Yasuda S, Ohmiya K, et al. Sequence analysis and overexpression
of a pectin lyase gene (pel1) from Aspergillus oryzae KBN616. Biosci Biotechnol
Biochem. 2001, 65, 209-212.
[79] Kitamoto N, Yoshino S, Ohmiya K, et al. Purification and characterization of the
overexpressed Aspergillus oryzae xylanase, XynF1. Biosci Biotechnol Biochem. 1999, 63,
1791-1794.
[80] Schnabel A, Cotinguiba F, Athmer B, Yang C, Westermann B, Schaks A, Porzel A, Brandt
W, Schumacher F, Vogt T. A piperic acid CoA ligase produces a putative precursor of
piperine, the pungent principle from black pepper fruits. Plant J. 2020, 102, 569-581.
[81] Wei J, Zhang Y, Yu TY, Sadre-Bazzaz K, Rudolph MJ, Amodeo GA, Symington LS, Walz
T, Tong L. A unified molecular mechanism for the regulation of acetyl-CoA carboxylase
by phosphorylation. Cell Discov. 2016, 29, 16044.
[82] Usaite R, Jewett MC, Oliveira AP, Yates JR 3rd, Olsson L, Nielsen J. Reconstruction of
the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator. Mol
Syst Biol. 2009, 5, 319.
[83] Dhingra S, Cramer RA. Regulation of Sterol Biosynthesis in the Human Fungal Pathogen
Aspergillus fumigatus: Opportunities for Therapeutic Development. Front Microbiol.
2017, 8, 92.
[84] Zhang J, Olsson L, Nielsen J. The beta-subunits of the Snf1 kinase in Saccharomyces
cerevisiae, Gal83 and Sip2, but not Sip1, are redundant in glucose derepression and
regulation of sterol biosynthesis. Mol Microbiol. 2010, 77, 371-383.
[85] Wells JM, Cole RJ, Kirksey JW. Emodin, a toxic metabolite of Aspergillus wentii isolated
from weevil-damaged chestnuts. Appl Microbiol. 1975, 30, 26-28.
[86] Widstrom R. L., Norris A. W., Spector A. A. Binding of cytochrome P450 monooxygenase
and lipoxygenase pathway products by heart fatty acid-binding protein. Biochemistry.
2001, 40, 1070–1076.
[87] Frandsen RJ, Schütt C, Lund BW, et al. Two novel classes of enzymes are required for
the biosynthesis of aurofusarin in Fusarium graminearum. J Biol Chem. 2011, 286,
10419-10428.
117
[88] Tian-Shung Wu, Jyh-Her Yeh, Pei-Lin Wu. The heartwood constituents of Tetradium
glabrifolium. Phytochemistry. 1995, 40, 121-124.
[89] Jang DS, Park EJ, Kang YH, et al. Compounds obtained from sida acuta with the potential
to induce quinone reductase and to inhibit 7,12-dimethylbenz[a]anthracene-induced
preneoplastic lesions in a mouse mammary organ culture model. Arch Pharm Res. 2003,
26, 585-590.
[90] Demir AS, Seşenoglu O, Dünkelmann P, Müller M. Benzaldehyde lyase-catalyzed
enantioselective carboligation of aromatic aldehydes with mono- and dimethoxy
acetaldehyde. Org Lett. 2003, 5, 2047-2050.
[91] Kelley LA, Mezulis S, Yates CM, et al. The Phyre2 web portal for protein modeling,
prediction and analysis. Nat Protoc. 2015, 10, 845-858.
[92] Tseng KL, Lee YZ, Chen YR, Lyu PC. 1H, 15N and 13C resonance assignments of light
organ-associated fatty acid-binding protein of Taiwanese fireflies. Biomol NMR Assign.
2016. 10. 71-74.
[93] Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases
and potential as drug targets. Nat Rev Drug Discov. 2008, 7, 489-503.
[94] Chmurzyńska A. The multigene family of fatty acid-binding proteins (FABPs): function,
structure and polymorphism. J Appl Genet. 2006, 47, 39-48.
[95] Li J, Henry E, Wang L, et al. Comparative study of the fatty acid binding process of a new
FABP from Cherax quadricarinatus by fluorescence intensity, lifetime and anisotropy.
PLoS One. 2012, 7, e51079.
[96] Folli C, Ramazzina I, Percudani R, Berni R. Ligand-binding specificity of an invertebrate
(Manduca sexta) putative cellular retinoic acid binding protein. Biochim Biophys Acta.
2005, 1747, 229-237.
[97] Liu JW, Almaguel FG, Bu L, et al. Expression of E-FABP in PC12 cells increase neurite
extension during differentiation involvement of n-3 and n-6 fatty acids. J Neurcochem.
2008, 106, 2015-2029.
[98] Ingram-Smith C, Smith KS. AMP-forming acetyl-CoA synthetases in Archaea show
unexpected diversity in substrate utilization. Archaea. 2007, 2, 95-107.
118
[99] Peng K, Chen F, She X, Yang C, Cui Y, Pan X. Selective oxidation of benzylic or allylic
hydroxyl group of sec-1,2-diols. Tetrahedron Letters. 2005, 46, 1217-1220.
[100]
Trivedi OA, Arora P, Sridharan V, et al. Enzymic activation and transfer of fatty
acids as acyl-adenylates in Mycobacteria. Nature. 2004, 428, 441-445.
[101]
Hayashi T, Kitamura Y, Funa N, et al. Fatty acyl-AMP ligase involvement in the
production of alkylresorcylic acid by a Myxococcus xanthus type III polyketide synthase.
Chembiochem. 2011, 12, 2166-76.
[102]
Zhang W, Du L, Qu Z, et al. Compartmentalized biosynthesis of mycophenolic acid.
Proc Natl Acad Sci USA. 2019, 116, 13305-13310.
[103]
Bartoszewska M, Opaliński L, Veenhuis M, van der Klei IJ. The significance of
peroxisomes in secondary metabolite biosynthesis in filamentous fungi. Biotechnol Lett.
2011, 33, 1921-1931.
[104]
Cary JW, Uka V, Han Z, Buyst D, et al. An Aspergillus flavus secondary metabolic
gene cluster containing a hybrid PKS-NRPS is necessary for synthesis of the 2-pyridones,
leporins. Fungal Genet Biol. 2015, 81, 88-97.
[105]
Ohashi M, Liu F, Hai Y, et al. SAM-dependent enzyme-catalysed pericyclic reactions
in natural product biosynthesis. Nature. 2017, 549, 502-506.
[106]
TePaske MR, Gloer JB, Wicklow DT, Dowd PF. Leporin A: an antiinsectan N-
alkoxypyridone from the sclerotia of Aspergillus leporis. Tetrahedron Letters. 1991, 32,
5687-5690.
[107]
Fujii R, Minami A, Tsukagoshi T, Sato N, Sahara T, Ohgiya S, Gomi K, Oikawa H.
Total biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA polymerase α:
heterologous expression of four biosynthetic genes in Aspergillus oryzae. Biosci
Biotechnol Biochem. 2011, 75, 1813-1817.
[108]
Nagamine S, Liu C, Nishishita J, Kozaki T, Sogahata K, Sato Y, Minami A, Ozaki T,
Schmidt-Dannert C, Maruyama JI, Oikawa H. Ascomycete Aspergillus oryzae Is an
Efficient Expression Host for Production of Basidiomycete Terpenes by Using Genomic
DNA Sequences. Appl Environ Microbiol. 2019, 85, e00409-19.
[109]
Araki Y, Yuzuki M, Masakari Y, et al. High-level heterologous protein production
119
using an attenuated selection marker in Aspergillus sojae. J Gen Appl Microbiol. 2020.
doi: 10.2323/jgam.2020.05.002.
[110]
Katayama T, Tanaka Y, Okabe T, et al. Development of a genome editing technique
using the CRISPR/Cas9 system in the industrial filamentous fungus Aspergillus oryzae.
Biotechnol Lett. 2016, 38, 637-642.
[111]
Nagamine S, Liu C, Nishishita J, et al. Ascomycete Aspergillus oryzae Is an Efficient
Expression Host for Production of Basidiomycete Terpenes by Using Genomic DNA
Sequences. Appl Environ Microbiol. 2019, 85, e00409-19.
[112]
Nicholson MJ, Koulman A, Monahan BJ, Pritchard BL, Payne GA, Scott B.
Identification of two aflatrem biosynthesis gene loci in Aspergillus flavus and metabolic
engineering of Penicillium paxilli to elucidate their function. Appl Environ Microbiol.
2009, 75, 7469-7481.
[113]
Watson AJ, Fuller LJ, Jeenes DJ, Archer DB. Homologs of aflatoxin biosynthesis
genes and sequence of aflR in Aspergillus oryzae and Aspergillus sojae. Appl Environ
Microbiol. 1999, 65, 307-310.
[114]
Bayram O, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O, Braus-
Stromeyer S, Kwon NJ, Keller NP, Yu JH, Braus GH. VelB/VeA/LaeA complex
coordinates light signal with fungal development and secondary metabolism. Science.
2008, 320, 1504-1506.
120
原著論文
Kan E, Katsuyama Y, Maruyama JI, Tamano K, Koyama Y, Ohnishi Y. Production of the plant
polyketide curcumin in Aspergillus oryzae: strengthening malonyl-CoA supply for yield
improvement. Biosci Biotechnol Biochem. 2019, 83, 1372-1381.
Kan E, Katsuyama Y, Maruyama JI, Tamano K, Koyama Y, Ohnishi Y. Efficient heterologous
production of atrochrysone carboxylic acid-related polyketides in an Aspergillus oryzae host
with enhanced malonyl-coenzyme A supply. J Gen Appl Microbiol. 2020, 66, 195-199.
Kan E, Tomita H, Katsuyama Y, Maruyama JI, Koyama Y, Ohnishi Y. Discovery of the 2,4'Dihydroxy-3'-methoxypropiophenone
Biosynthesis
Chembiochem. 2021, 22, 203-211.
121
Genes
in
Aspergillus
oryzae.
付録
コドン最適化 4CL 塩基配列（5’-3’）
ATGGACACCCAGACCAAAACCGACCAGAAAGACATCATCTTCCGTTCTAAACTGCCGGACATCT
ACATCCCGAAACACCTGCCGCTGCACTCTTACTGCGGTGAAAACATCTCTCAGTTCTCTTCTCG
TCCGTGCCTGATCAACGGTTCTAATGATCGTGTATACACCTACGCAGAAGTTGAAATCACCTCT
CGTAAAGTTGCTGCTGGTCTGCACAAACACGGTATCAAACAGACCGAAACCATCATGCTGCTG
CTGCCGAACTGCCCGGAATTCGTTTTCGCTTTCCTGGGTGCTTCTTACATCGGTGCTGTTTCT
ACCACCGCTAACCCGTTCTTCACCTCTTCTGAAATCATCAAACAGGCTAAAGCTTCTAAAACCA
AACTGATCATCACCGTTTCTACCACCGTTCCGAAACTGAAAGACTTCTCTCAGGAAAACCACGT
TAAAATCATGTGCATCGACGACAAAATCGACGGTTGCCTGCACTTCTCTTCTGACCTGGAAAAC
TCTGACGAAACCACCCTGCCGGACGTTGAAATCCGTCCGGACGACGTTGTTGCTCTGCCGTAC
TCTTCTGGTACCACCGGCCTGCCGAAAGGTGTTATGCTGACCCACAAAGGcCTGGTTACCTCT
GTTGCTCAGCAGGTTGACGGTGACAACGCTAACCTGTACATGCACCACGAgGACGTTGTTATG
TGCACCCTGCCGCTGTTCCACATCTACTCTATGAACTCTATCCTGCTGTGCGGTCTGCGTGTT
GGTGCTGCTATCCTGCTGATGCACAAATTCGAAATCGTTACCTTCCTGGAACTGATCCAGCGT
TACAAAGTTACCATCGGTCCATTCGTTCCGCCGATCGTTCTGGCTATCGCTAAATCTAACGTT
GTTGACCAGTACGACCTGTCTACCGTTCGTACCGTTATGTCTGGTGCTGCTCCGCTGGGTTCT
GAACTGGAAGACGCTGTTCGTGCTAAATTCCCGAACGCTAAACTGGGTCAGGGTTACGGTATG
ACCGAAGCTGGTCCGGTTCTCGCTATGTGCCTGGCGTTCGCTAAAGAACCATTCGAAATCAAA
TCTGGTGCTTGCGGTACCGTTGTTCGTAACTCTGAAATGAAAATCATCGACACCGAAACCGGC
GCTTCTCTGCCGCGTAACCAGTCTGGTGAAATCTGCATCCGTGGTGACCAGATCATGAAAGGT
TACCTGAACGACCCGGAAGCTACCGAACGTACCATCGACAAAGAAGGTTGGCTGCACACCGGC
GACATCGGTTACATCGACGACGACGACGAACTGTTCATCGTTGACCGTCTGAAAGAACTGATC
AAATACAAAGGTTTCCAGGTTGCTCCGCCGGAACTGGAAGCTCTGCTGGTTCCACATCCGAAC
GTAAGCGACGCTGCTGTTGTTTCTATGAAAGACGAAGGTGCTGGTGAAGTTCCGGTTGCTTTC
GTTGTTCGTTCTAACGGTTCTACCACCACCGAAGACGAAATCAAACAGTTCGTTTCTAAACAGG
TTATCTTCTACAAACGTATCAACCGTGTTTTCGGTGTTGACTCTATCCCGAAATCTCCGTCTGG
TAAAATCGTTCGTAAAGACCTGCGTGCTAAACTGGCTGCTCGTTTCCTGAACGGTCCAACCAC
CAACGTTGTTCCGAACGGTGGTAACGTTGCTAAAGACAACGTTCCAAATGGTGTAAGCAACGG
TGTTTCTAAAGCTAACGGTGGTGTTGCTAAAGAAGGTGTTGCTAACGGTGTTCCGACCGACGG
TGACTACGGTGTTGCTACCAAAGGTGTTGCTAACGGTATCTCTAACGGTGTTTACAAACAGGT
TTCTAACGGTGTTGTTTCTAACGGTGTTGCTAACGGTATCGTTTCTAACGGTATCGCTAACGG
TGTTCACAACTAG
122
コドン最適化 TAL 塩基配列（5’-3’）
ATGAGCCATCCCTACATTGCGTGCCGGGCGTTCCCTATCTCAGCCAGAAACATTGGGGGTCAAGACTCGT
GGGCGACGGGCGAAAAGGGCGTTCATAAGGTCACCACTATGAAGATCGATGGTCGCGGACTCACCATCT
CGCAGACTGTTGCCGCTGCCTCTCGTGAGGGTAGCGAATTCGCTGTCTCGGAGGACGCCCTCCGTGCTAT
GAACGCCTCCCGGAATCTGAAGCTTGAAATCCTGGCCACCGGCAAGCCAATCTACGGTGTTACCACTGG
CTTCGGTGATTCTGTCAACCGTCAGATCAGCCCGGAGAAGACTGCCCGCCTTCAGAACGAATTGATCCGT
TATCACCTCAATGGAACTGGACGCCTCGCCTCCGATGAGGTTGTGCGCGCCACTGTCCTTATCCGTGCTA
ACTGCTTGGCCCGGGGAAATTCGGGCGTGTCCCTTCCTGTTGTCGAGCTCCTGCTTGATTTCCTTAAGCAT
GACATCTTGCCTACCGTTCCTGAACGTGGTTCTGTTGGAGCTTCCGGCGATTTGGTTCCCCTCTGTTACCT
GGCCTATGCTCTCACAGGCCAGGGAAAGGTCCGTCACCGCGGCGAAACCCGCCCTACTGCTGAGGTCCT
CGCCGAATTGGGACTCAAGCCGGTGACCCTGGAAGCTAAGGACGGACTGGCCCTTATCAACGGCACCTC
GTTCTCCGCTGCCTTCGCCGTGCTTAATACTGAGGCTGCCGCTGAATTGGCTGATGTTGCCGACATCTGCA
CTGCCCTCGCTTCTGAGGGTATGCTGGGAAACCGTGGCCATTACGCTCCTTTCATCCATAATGAAAAGCCT
CACTCTGGACAGGGTGCCTCCGCTGCTTACATCCACCAGATGCTCGAGGGATCCTCTCTGGCTATGACCT
ATGATCAGGTGGTTGACCTCAACGTCCCACTGGATGGCCGCCATTACCAGCGTCTTACTCGGTCGATCCA
GGACCGGTATTCCTTGCGCTGTGCCCCGCACGTGAATGGCGTTCTTCGGGATATGTTGGACTGGGTGCGC
ACCTGGATGACTGTTGAAATCAACAGCTCGTCCGATAATCCACTGTTCGACCCGTCTACCGGTGCTGTCT
ACAGCGGCGGTAACTTCTATGGAGGCCATGTCGTGACCGCCATGGATTCCCTTAAGACTGCCGTGGCTGG
AATCGCTGATTTGCTCGACCGGCAGTTGGCCCTGCTTGTTGACGAGAAGTTCAACAATGGCCTCACCCCT
AATCTGATCGCTCGCGTCGATGACGATGACACTGAAGCCGGCCTCCAGCACGGTTTCAAGGGAATGCAG
ATCGCTTGCTCTAGCCTTACCGCCGAGGCTTTGAAGCATTCTGGCCCTGCCTCCACCTTCTCTCGCAGCAC
TGAAGCCCACAACCAGGATAAGGTGTCTATGGCTCCAATTGCTGCTCGTGATGCTCGTACTGTCATCGAG
CTCACTCGTGAAGTGGCCGCTATCCATTTGCTCGCCGCTTGTCAGGCTGTTGAGCTGCGTGGAGTGGATG
AAATGAGCCCTCGGACTAAGGCTGTGCACGCCCGTATCCGTAAGGAAGTCCCCTTCGCCGCTAAGGACC
GCCAGATGGATGGTGACATCGCCGCTGTTGTTGAGATGATTGCGTCTGGGGCTATTACCGAAGCAGCACG
AGCGGGAGGAAACCTGTAG
123
pksc2-pksc8 領域の欠失確認
124
Compound 9 (1H NMR)
Compound 9 (13C NMR)
125
Compound 9 (H-H COSY)
Compound 9 (HMBC)
126
Compound 9 (HMQC)
127
Purified 11 (1H NMR)
Authentic 11 (1H NMR)
128
180.0
170.0
160.0
150.0
140.0
130.0
120.0
110.0
100.0
X : parts per Million : Carbon13
129
90.0
80.0
70.0
60.0
50.0
43.116
41.872
41.029
40.617
40.522
40.426
40.282
40.148
40.005
39.870
39.727
39.593
37.304
31.837
29.558
29.252
27.347
22.645
18.356
14.516
190.0
70.299
132.257
130.687
127.786
127.662
126.905
(thousandths)
1.0
2.0
Compound 13 (1H NMR)
Compound 13 (13C NMR)
40.0
30.0
20.0
10.0
Compound 13 (H-H COSY)
Y : parts per Million : Carbon13
190.0
170.0
150.0
130.0
110.0
90.0
70.0
50.0
30.0
10.0
abundance
Compound 13 (HMBC)
9.0
8.0
X : parts per Million : Proton
7.0
6.0
5.0
4.0
3.0
130
2.0
1.0
1.0 2.0
(thousandths)
3.0
Y : parts per Million : Carbon13
200.0
100.0
abundance
0 0.2 0.4 0.6
Compound 13 (HMQC)
8.0
7.0
X : parts per Million : Proton
6.0
5.0
4.0
131
3.0
2.0
1.0
0 1.0 2.0
(thousandths)
謝辞
本研究を行うにあたり、東京大学で受託研究員として研究させていただくとともに、終始懇
切なご指導・ご助言を頂きました東京大学大学院農学生命科学研究科
醗酵学研究室教授
大西康夫先生に深甚なる謝意を申し上げます。
醗酵学研究室 准教授 勝山陽平先生には、本研究の開始時から代謝産物の解析、構造解析
など研究に関して懇切丁寧なご指導・ご助言を賜るとともに、研究の方向性から文書の作成
方法に至るまで多くのことを学ばせていただきました。ここに深く感謝申し上げます。
醸造微生物学（キッコーマン）寄付講座 特任准教授 丸山潤一先生には、麹菌の組換え操
作から麹菌研究に関する様々なご助言ならびにご支援を賜るとともに、研究に関する様々
なご相談をさせていただきました。ここに深く感謝申し上げます。
研究室での進捗報告会では微生物潜在酵素（天野エンザイム）寄付講座
特任教授
尾仲
宏康先生、特任講師 浅水俊平先生、現・微生物膜輸送工学（発酵研究所）寄付研究部門 川
崎寿先生には大変貴重なご助言を賜りました。ここに深く感謝申し上げます。
産業技術総合研究所
玉野孝一先生には麹菌の代謝改変に関して大変貴重なご助言をいた
だきました。ここに深く感謝申し上げます。
理化学研究所
長田裕之先生、二村友史先生には単離化合物の生物活性評価を行っていた
だきました。ここに深く感謝申し上げます。
醗酵学研究室の皆様には、会社から来た私を温かく迎え入れていただき、研究生活を送るに
あたり大変お世話になりました。冨田宏矢博士、角田毅博士には研究に関する多くの有意義
な議論をさせていただくとともに、些細な相談もさせていただきました。醗酵学研究室の皆
様に厚く御礼を申し上げます。
本研究に挑戦する機会を与えていただきましたキッコーマン株式会社
取締役常務執行役
員 松山旭博士に深く感謝申し上げます。また、本研究テーマを進めるにあたり多大なご助
言ご指導を賜りました野田産業科学研究所 小山泰二博士に深く感謝いたします。また、麹
菌に対する知識のない私に様々なご助言をいただきました、高橋理博士、小川真弘博士をは
じめ同研究所の皆様に厚く御礼申し上げます。
132
最後にこれまでの研究生活を支えてくれた両親、祖父母ならびに妻に心から感謝いたしま
す。
133
...
論文の公開元へ
