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Article ; Online: Anthranilate-activating modules from fungal nonribosomal peptide assembly lines.

Ames, Brian D / Walsh, Christopher T

2010 Volume 49, Issue 15, Page(s) 3351–3365

Abstract: Fungal natural products containing benzodiazepinone- and quinazolinone-fused ring systems can be assembled by nonribosomal peptide synthetases (NRPS) using the conformationally restricted beta-amino acid anthranilate as one of the key building blocks. We ...

Abstract	Fungal natural products containing benzodiazepinone- and quinazolinone-fused ring systems can be assembled by nonribosomal peptide synthetases (NRPS) using the conformationally restricted beta-amino acid anthranilate as one of the key building blocks. We validated that the first module of the acetylaszonalenin synthetase of Neosartorya fischeri NRRL 181 activates anthranilate to anthranilyl-AMP. With this as a starting point, we then used bioinformatic predictions about fungal adenylation domain selectivities to identify and confirm an anthranilate-activating module in the fumiquinazoline A producer Aspergillus fumigatus Af293 as well as a second anthranilate-activating NRPS in N. fischeri. This establishes an anthranilate adenylation domain code for fungal NRPS and should facilitate detection and cloning of gene clusters for benzodiazepine- and quinazoline-containing polycyclic alkaloids with a wide range of biological activities.
MeSH term(s)	Amino Acid Sequence ; Aspergillus fumigatus/genetics ; Aspergillus fumigatus/metabolism ; Carbon Radioisotopes ; Cloning, Molecular ; DNA Primers ; Fungal Proteins/biosynthesis ; Fungal Proteins/chemistry ; Fungal Proteins/genetics ; Fungi/genetics ; Fungi/metabolism ; Isotope Labeling/methods ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Open Reading Frames ; Recombinant Proteins/chemistry ; ortho-Aminobenzoates/metabolism
Chemical Substances	Carbon Radioisotopes ; DNA Primers ; Fungal Proteins ; Recombinant Proteins ; ortho-Aminobenzoates ; anthranilic acid (0YS975XI6W)
Language	English
Publishing date	2010-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi100198y
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Article ; Online: Aminobenzoates as building blocks for natural product assembly lines.

Walsh, Christopher T / Haynes, Stuart W / Ames, Brian D

Natural product reports

2012 Volume 29, Issue 1, Page(s) 37–59

Abstract: The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta- ... ...

Abstract	The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta-isomer is not available by that route and starts from UDP-3-aminoglucose. PABA is largely funnelled into folate biosynthesis while anthranilate is the scaffold for biosynthetic elaboration into many natural heterocycles, most notably with its role in indole formation for tryptophan biosynthesis. Anthranilate is also converted to benzodiazepinones, fumiquinazolines, quinoxalines, phenoxazines, benzoxazolinates, quinolones, and phenazines, often with redox enzyme participation. The 5-hydroxy form of 3-aminobenzaote is the starter unit for ansa-bridged rifamycins, ansamitocins, and geldanamycins, whereas regioisomers 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-3-aminobenzoate are key components of antimycin, grixazone, and platencin and platensimycin biosynthesis, respectively. The enzymatic mechanisms for generation of the aminobenzoate regioisomers and their subsequent utilization for diverse heterocycle and macrocycle construction are examined.
MeSH term(s)	4-Aminobenzoic Acid/chemistry ; 4-Aminobenzoic Acid/metabolism ; Biological Products/chemistry ; Biological Products/metabolism ; Biological Products/pharmacology ; Chorismic Acid/chemistry ; Chorismic Acid/metabolism ; Molecular Structure ; Stereoisomerism ; ortho-Aminobenzoates/chemistry ; ortho-Aminobenzoates/metabolism ; para-Aminobenzoates
Chemical Substances	Biological Products ; ortho-Aminobenzoates ; para-Aminobenzoates ; Chorismic Acid (GI1BLY82Y1) ; 4-Aminobenzoic Acid (TL2TJE8QTX)
Language	English
Publishing date	2012-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2002546-4
ISSN	1460-4752 ; 0265-0568
ISSN (online)	1460-4752
ISSN	0265-0568
DOI	10.1039/c1np00072a
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Article ; Online: Insight into the molecular basis of aromatic polyketide cyclization: crystal structure and in vitro characterization of WhiE-ORFVI.

Lee, Ming-Yue / Ames, Brian D / Tsai, Shiou-Chuan

Biochemistry

2012 Volume 51, Issue 14, Page(s) 3079–3091

Abstract: Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled ... ...

Abstract	Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled polyketide chain catalyzed by aromatase/cyclase (ARO/CYC), which serves as a key control point in aromatic ring formation. How different ARO/CYCs promote different cyclization patterns is not well understood. The whiE locus of Streptomyces coelicolor A3(2) is responsible for the biosynthesis of an aromatic polyketide precursor to the gray spore pigment. The WhiE ARO/CYC catalyzes the regiospecific C9-C14 and C7-C16 cyclization and aromatization of a 24-carbon polyketide chain. WhiE ARO/CYC shares a high degree of similarity to another nonreducing PKS ARO/CYC, TcmN ARO/CYC. This paper presents the apo crystal structure of WhiE ARO/CYC, and cocrystal structures of WhiE and TcmN ARO/CYCs bound with polycyclic aromatic compounds that mimic the respective ARO/CYC products. Site-directed mutagenesis coupled with in vitro PKS reconstitution assays was used to characterize the interior pocket residues of WhiE ARO/CYC. The results confirmed that the interior pocket of ARO/CYCs is a critical determinant of polyketide cyclization specificity. A unified ARO/CYC-mediated cyclization mechanism is proposed on the basis of these structural and functional results.
MeSH term(s)	Amino Acid Sequence ; Aromatase/chemistry ; Aromatase/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Crystallography, X-Ray ; Cyclization ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Polyketide Synthases/chemistry ; Polyketide Synthases/metabolism ; Polyketides/chemistry ; Polyketides/metabolism ; Protein Conformation ; Sequence Alignment ; Streptomyces coelicolor/enzymology ; Streptomyces coelicolor/metabolism
Chemical Substances	Bacterial Proteins ; Polyketides ; Polyketide Synthases (79956-01-7) ; Aromatase (EC 1.14.14.1)
Language	English
Publishing date	2012-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi201705q
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Article ; Online: Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis.

Zhang, Wenjun / Ames, Brian D / Walsh, Christopher T

Biochemistry

2011 Volume 50, Issue 24, Page(s) 5401–5403

Abstract: Phenylalanine hydroxylase (PheH) is an iron(II)-dependent enzyme that catalyzes the hydroxylation of aromatic amino acid l-phenylalanine (L-Phe) to l-tyrosine (L-Tyr). The enzymatic modification has been demonstrated to be highly regiospecific, forming ... ...

Abstract	Phenylalanine hydroxylase (PheH) is an iron(II)-dependent enzyme that catalyzes the hydroxylation of aromatic amino acid l-phenylalanine (L-Phe) to l-tyrosine (L-Tyr). The enzymatic modification has been demonstrated to be highly regiospecific, forming proteinogenic para-Tyr (p-Tyr) exclusively. Here we biochemically characterized the first example of a phenylalanine 3-hydroxylase (Phe3H) that catalyzes the synthesis of meta-Tyr (m-Tyr) from Phe. Subsequent mutagenesis studies revealed that two residues in the active site of Phe3H (Cys187 and Thr202) contribute to C-3 rather than C-4 hydroxylation of the phenyl ring. This work sets the stage for the mechanistic and structural study of regiospecific control of the substrate hydroxylation by PheH.
MeSH term(s)	Amino Acid Substitution ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Catalytic Domain/genetics ; Humans ; Isomerism ; Kinetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Phenylalanine Hydroxylase/chemistry ; Phenylalanine Hydroxylase/genetics ; Phenylalanine Hydroxylase/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Streptomyces/enzymology ; Streptomyces/genetics ; Tyrosine/biosynthesis ; Tyrosine/chemistry
Chemical Substances	Bacterial Proteins ; Recombinant Proteins ; Tyrosine (42HK56048U) ; 3-tyrosine (D5YF57V4QW) ; Phenylalanine Hydroxylase (EC 1.14.16.1)
Language	English
Publishing date	2011-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi200733c
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Article ; Online: Enzymatic processing of fumiquinazoline F: a tandem oxidative-acylation strategy for the generation of multicyclic scaffolds in fungal indole alkaloid biosynthesis.

Ames, Brian D / Liu, Xinyu / Walsh, Christopher T

Biochemistry

2010 Volume 49, Issue 39, Page(s) 8564–8576

Abstract: Aspergillus fumigatus Af293 is a known producer of quinazoline natural products, including the antitumor fumiquinazolines, of which the simplest member is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic acid, tryptophan, and ... ...

Abstract	Aspergillus fumigatus Af293 is a known producer of quinazoline natural products, including the antitumor fumiquinazolines, of which the simplest member is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic acid, tryptophan, and alanine. FQF is the proposed biological precursor to fumiquinazoline A (FQA) in which the pendant indole side chain has been modified via oxidative coupling of an additional molecule of alanine, yielding a fused 6-5-5 imidazoindolone. We recently identified fungal anthranilate-activating nonribosomal peptide synthetase (NRPS) domains through bioinformatics approaches. One domain previously identified is part of the trimodular NRPS Af12080, which we predict is responsible for FQF formation. We now show that two adjacent A. fumigatus ORFs, a monomodular NRPS Af12050 and a flavoprotein Af12060, are necessary and sufficient to convert FQF to FQA. Af12060 oxidizes the 2',3'-double bond of the indole side chain of FQF, and the three-domain NRPS Af12050 activates l-Ala as the adenylate, installs it as the pantetheinyl thioester on its carrier protein domain, and acylates the oxidized indole for subsequent intramolecular cyclization to create the 6-5-5 imidazolindolone of FQA. This work provides experimental validation of the fumiquinazoline biosynthetic cluster of A. fumigatus Af293 and describes an oxidative annulation biosynthetic strategy likely shared among several classes of polycyclic fungal alkaloids.
MeSH term(s)	Acylation ; Aspergillus fumigatus/enzymology ; Aspergillus fumigatus/genetics ; Cloning, Molecular ; Fungal Proteins/genetics ; Fungal Proteins/isolation & purification ; Fungal Proteins/metabolism ; Genes, Fungal ; Indole Alkaloids/metabolism ; Open Reading Frames ; Oxidative Coupling ; Quinazolines/metabolism ; Tryptophan/analogs & derivatives ; Tryptophan/metabolism
Chemical Substances	Fungal Proteins ; Indole Alkaloids ; Quinazolines ; fumiquinazoline A ; fumiquinazoline F ; Tryptophan (8DUH1N11BX)
Language	English
Publishing date	2010-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi1012029
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Article: Insight into the Molecular Basis of Aromatic Polyketide Cyclization: Crystal Structure and in Vitro Characterization of WhiE-ORFVI

Lee, Ming-Yue / Ames Brian D / Tsai Shiou-Chuan

Biochemistry. 2012 Apr. 10, v. 51, no. 14

2012

Abstract	Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled polyketide chain catalyzed by aromatase/cyclase (ARO/CYC), which serves as a key control point in aromatic ring formation. How different ARO/CYCs promote different cyclization patterns is not well understood. The whiE locus of Streptomyces coelicolor A3(2) is responsible for the biosynthesis of an aromatic polyketide precursor to the gray spore pigment. The WhiE ARO/CYC catalyzes the regiospecific C9âC14 and C7âC16 cyclization and aromatization of a 24-carbon polyketide chain. WhiE ARO/CYC shares a high degree of similarity to another nonreducing PKS ARO/CYC, TcmN ARO/CYC. This paper presents the apo crystal structure of WhiE ARO/CYC, and cocrystal structures of WhiE and TcmN ARO/CYCs bound with polycyclic aromatic compounds that mimic the respective ARO/CYC products. Site-directed mutagenesis coupled with in vitro PKS reconstitution assays was used to characterize the interior pocket residues of WhiE ARO/CYC. The results confirmed that the interior pocket of ARO/CYCs is a critical determinant of polyketide cyclization specificity. A unified ARO/CYC-mediated cyclization mechanism is proposed on the basis of these structural and functional results.
Keywords	Streptomyces coelicolor ; aromatase ; biosynthesis ; crystal structure ; drugs ; loci ; polyketides ; site-directed mutagenesis ; spores
Language	English
Dates of publication	2012-0410
Size	p. 3079-3091.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi201705q
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Short pathways to complexity generation: fungal peptidyl alkaloid multicyclic scaffolds from anthranilate building blocks.

Walsh, Christopher T / Haynes, Stuart W / Ames, Brian D / Gao, Xue / Tang, Yi

ACS chemical biology

2013 Volume 8, Issue 7, Page(s) 1366–1382

Abstract: Complexity generation in naturally occurring peptide scaffolds can occur either by posttranslational modifications of nascent ribosomal proteins or through post assembly line tailoring of nonribosomal peptides. Short enzymatic pathways utilizing ... ...

Abstract	Complexity generation in naturally occurring peptide scaffolds can occur either by posttranslational modifications of nascent ribosomal proteins or through post assembly line tailoring of nonribosomal peptides. Short enzymatic pathways utilizing bimodular and trimodular nonribosomal peptide synthetase (NRPS) assembly lines, followed by tailoring oxygenases and/or prenyltransferases, efficiently construct complex fungal peptidyl alkaloid scaffolds in Aspergilli, Neosartorya, and Penicillium species. Use of the nonproteinogenic amino acid anthranilate as chain-initiating building block and chain-terminating intramolecular nucleophile leads efficiently to peptidyl alkaloid scaffolds with two to seven fused rings.
MeSH term(s)	Alkaloids/chemistry ; Fungi/chemistry ; Gliotoxin/chemistry ; Indoles/chemistry ; Molecular Structure ; Peptide Synthases/chemistry ; Peptides/chemistry ; Piperazines/chemistry ; Spiro Compounds/chemistry ; ortho-Aminobenzoates/chemistry
Chemical Substances	Alkaloids ; Indoles ; Peptides ; Piperazines ; Spiro Compounds ; ortho-Aminobenzoates ; anthranilic acid (0YS975XI6W) ; brevianamide A (23402-09-7) ; Gliotoxin (67-99-2) ; tryptoquivaline (CW5S8OP3VO) ; Peptide Synthases (EC 6.3.2.-) ; non-ribosomal peptide synthase (EC 6.3.2.-)
Language	English
Publishing date	2013-06-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/cb4001684
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Article: Aminobenzoates as building blocks for natural product assembly lines

Walsh, Christopher T. / Haynes, Stuart W. / Ames, Brian D.

Natural product reports. 2011 Dec. 7, v. 29, no. 1

2011

Abstract: Covering: up to the end of September 2011 The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate ... ...

Abstract	Covering: up to the end of September 2011 The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta-isomer is not available by that route and starts from UDP-3-aminoglucose. PABA is largely funnelled into folate biosynthesis while anthranilate is the scaffold for biosynthetic elaboration into many natural heterocycles, most notably with its role in indole formation for tryptophan biosynthesis. Anthranilate is also converted to benzodiazepinones, fumiquinazolines, quinoxalines, phenoxazines, benzoxazolinates, quinolones, and phenazines, often with redox enzyme participation. The 5-hydroxy form of 3-aminobenzaote is the starter unit for ansa-bridged rifamycins, ansamitocins, and geldanamycins, whereas regioisomers 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-3-aminobenzoate are key components of antimycin, grixazone, and platencin and platensimycin biosynthesis, respectively. The enzymatic mechanisms for generation of the aminobenzoate regioisomers and their subsequent utilization for diverse heterocycle and macrocycle construction are examined.
Keywords	aminobenzoates ; biosynthesis ; chorismic acid ; enzymes ; folic acid ; indoles ; metabolites ; phenazines ; positional isomers ; quinolones ; quinoxalines ; rifamycins ; shikimate pathway ; tryptophan
Language	English
Dates of publication	2011-1207
Size	p. 37-59.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2002546-4
ISSN	1460-4752 ; 0265-0568
ISSN (online)	1460-4752
ISSN	0265-0568
DOI	10.1039/c1np00072a
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Article ; Online: Structural and biochemical characterization of ZhuI aromatase/cyclase from the R1128 polyketide pathway.

Ames, Brian D / Lee, Ming-Yue / Moody, Colleen / Zhang, Wenjun / Tang, Yi / Tsai, Shiou-Chuan

Biochemistry

2011 Volume 50, Issue 39, Page(s) 8392–8406

Abstract: Aromatic polyketides comprise an important class of natural products that possess a wide range of biological activities. The cyclization of the polyketide chain is a critical control point in the biosynthesis of aromatic polyketides. The aromatase/ ... ...

Abstract	Aromatic polyketides comprise an important class of natural products that possess a wide range of biological activities. The cyclization of the polyketide chain is a critical control point in the biosynthesis of aromatic polyketides. The aromatase/cyclases (ARO/CYCs) are an important component of the type II polyketide synthase (PKS) and help fold the polyketide for regiospecific cyclizations of the first ring and/or aromatization, promoting two commonly observed first-ring cyclization patterns for the bacterial type II PKSs: C7-C12 and C9-C14. We had previously reported the crystal structure and enzymological analyses of the TcmN ARO/CYC, which promotes C9-C14 first-ring cyclization. However, how C7-C12 first-ring cyclization is controlled remains unresolved. In this work, we present the 2.4 Å crystal structure of ZhuI, a C7-C12-specific first-ring ARO/CYC from the type II PKS pathway responsible for the production of the R1128 polyketides. Though ZhuI possesses a helix-grip fold shared by TcmN ARO/CYC, there are substantial differences in overall structure and pocket residue composition that may be important for directing C7-C12 (rather than C9-C14) cyclization. Docking studies and site-directed mutagenesis coupled to an in vitro activity assay demonstrate that ZhuI pocket residues R66, H109, and D146 are important for enzyme function. The ZhuI crystal structure helps visualize the structure and putative dehydratase function of the didomain ARO/CYCs from KR-containing type II PKSs. The sequence-structure-function analysis described for ZhuI elucidates the molecular mechanisms that control C7-C12 first-ring polyketide cyclization and builds a foundation for future endeavors into directing cyclization patterns for engineered biosynthesis of aromatic polyketides.
MeSH term(s)	Amino Acid Sequence ; Aromatase/metabolism ; Crystallography, X-Ray ; Models, Molecular ; Molecular Sequence Data ; Multienzyme Complexes/metabolism ; Mutagenesis, Site-Directed ; Polyketide Synthases/chemistry ; Polyketide Synthases/genetics ; Polyketide Synthases/metabolism ; Sequence Alignment ; Streptomyces/enzymology ; Streptomyces/genetics ; Substrate Specificity
Chemical Substances	Multienzyme Complexes ; Polyketide Synthases (79956-01-7) ; Aromatase (EC 1.14.14.1)
Language	English
Publishing date	2011-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi200593m
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Article ; Online: Unraveling terminal C-domain-mediated condensation in fungal biosynthesis of imidazoindolone metabolites.

Haynes, Stuart W / Ames, Brian D / Gao, Xue / Tang, Yi / Walsh, Christopher T

Biochemistry

2011 Volume 50, Issue 25, Page(s) 5668–5679

Abstract: The fungal peptidyl alkaloids of the tryptoquialanine and fumiquinazoline families are nonribosomally assembled by annulation of the indole side chain of fumiquinazoline F (FQF) with an alaninyl or aminoisobutyryl unit by monomodular NRPS enzymes ... ...

Abstract	The fungal peptidyl alkaloids of the tryptoquialanine and fumiquinazoline families are nonribosomally assembled by annulation of the indole side chain of fumiquinazoline F (FQF) with an alaninyl or aminoisobutyryl unit by monomodular NRPS enzymes containing adenylation, thiolation, and condensation (A-T-C) domains. The Af12060 and Af12050 enzyme pair from Aspergillus fumigatus thereby converts FQF to FQA, while the homologous TqaH and TqaB enzyme pair from Penicillium aethiopicum makes the 2'-epi diastereomer of FQA, differing only in the stereochemistry of one of the C-N bonds formed in the annulation with l-Ala. To evaluate the basis for this stereochemical control, we have mixed and matched the flavoprotein oxygenases Af12060 and TqaH with the A-T-C modular enzymes Af12050 and TqaB to show that the NRPS enzymes control the stereochemical outcome. The terminal 50 kDa condensation domains of Af12050 and TqaB are solely responsible for the stereochemical control as shown both by making chimeric (e.g., A-T-C* and A-T-C) forms of these monomodular NRPS enzymes and by expression, purification, and assay of the excised C-domains. The Af12050 and TqaB condensation domains are thus a paired set of diastereospecific annulation catalysts that act on the fumiquinazoline F scaffold.
MeSH term(s)	Alanine/chemistry ; Aspergillus fumigatus/enzymology ; Aspergillus fumigatus/genetics ; Aspergillus fumigatus/metabolism ; Catalytic Domain/genetics ; Chromatography, High Pressure Liquid/methods ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Imidazoles/chemical synthesis ; Imidazoles/metabolism ; Indoles/chemical synthesis ; Indoles/metabolism ; Mixed Function Oxygenases/chemical synthesis ; Mutant Chimeric Proteins/chemical synthesis ; Penicillium/enzymology ; Penicillium/genetics ; Penicillium/metabolism ; Peptide Synthases/biosynthesis ; Peptide Synthases/genetics ; Peptide Synthases/metabolism ; Quinazolines/chemical synthesis ; Quinazolines/metabolism ; Stereoisomerism
Chemical Substances	Imidazoles ; Indoles ; Mutant Chimeric Proteins ; Quinazolines ; fumiquinazoline A ; Mixed Function Oxygenases (EC 1.-) ; Peptide Synthases (EC 6.3.2.-) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2011-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi2004922
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