NDLI: Stereospecific Synthesis of threo- and erythro-β-Hydroxyglutamic Acid During Kutzneride Biosynthesis

Content Provider	PubMed Central
Author	Strieker, Matthias Nolan, Elizabeth M. Walsh, Christopher T. Marahiel, Mohamed A.
Abstract	The antifungal and antimicrobial kutznerides, hexadepsipeptides comprised of one α-hydroxy acid and five non-proteinogenic amino acids, are remarkable examples of the structural diversity found in nonribosomally-produced natural products. They contain D-3-hydroxyglutamic acid, which is found in the threo and erythro isomers in mature kutznerides. In this study, two putative non-heme iron oxygenase enzymes, KtzO and KtzP, were recombinantly expressed, characterized biochemically in vitro, and found to stereospecifically hydroxylate the β-position of glutamic acid. KtzO generates threo-L-hydroxyglutamic acid and KtzP catalyzes the formation of the erythro-isomer bound to the peptidyl carrier protein of the third module of the nonribosomal peptide synthetase KtzH. This module has a truncated adenylation domain and is unable to activate and incorporate glutamic acid. The lack of a functional adenylation domain in the third KtzH module is compensated in trans by the stand-alone adenylation domain KtzN, which activates and transfers glutamic acid onto the carrier of KtzH in the presence of the truncated adenylation domain and either KtzO or KtzP. A method that employs non-hydrolyzable coenzyme A analogs was developed and used to determine the kinetic parameters for KtzO- and KtzP-catalyzed hydroxylation of glutamic acid bound to the carrier protein. A detailed mechanism for the in trans compensation of the truncated adenylation domain and the stereospecific hydroxyglutamic acid generation and incorporation is presented. These insights may guide the use of KtzO/KtzP and KtzN or other in trans modification/restoration tools in biocombinatorial engineering approaches.
Related Links	http://dx.doi.org/10.1021/ja9054417
Ending Page	13530
Page Count	8
Starting Page	13523
File Format	PDF
ISSN	00027863
e-ISSN	15205126
Journal	Journal of the American Chemical Society
Issue Number	37
Volume Number	131
Language	English
Publisher Date	2009-09-23
Access Restriction	Open
Subject Keyword	Colloid and Surface Chemistry Biochemistry Chemistry(all) Catalysis Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Chemistry Colloid and Surface Chemistry Biochemistry Catalysis

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Stereospecific Cross-Coupling of Secondary Alkyl β-Trifluoroboratoamides

Stereospecific Synthesis and Characterization of Oligodeoxyribonucleotides Containing an N2 -(1-Carboxyethyl)-2′-deoxyguanosine

Toward β-Amino Acid Proteins: Design, Synthesis, and Characterization of a Fifteen Kilodalton β-Peptide Tetramer

Stereospecific decarboxylative allylation of sulfones

Cascade Reactions during Coronafacic Acid Biosynthesis: Elongation, Cyclization, and Functionalization during Cfa7-Catalyzed Condensation

Direct and Stereospecific Synthesis of Allenes via Reduction of Propargylic Alcohols with Cp2Zr(H)Cl

Tandem Action of the O2- and FADH2-Dependent Halogenases KtzQ and KtzR Produce 6,7-Dichlorotryptophan for Kutzneride Assembly

Halogenated β,γ-methylene- and ethylidene-dGTP-DNA ternary complexes with DNA polymerase β: structural evidence for stereospecific binding of the fluoromethylene analogues

Engineered Biosynthesis of Aklanonic Acid Analogs

Stereospecific Synthesis of threo- and erythro-β-Hydroxyglutamic Acid During Kutzneride Biosynthesis

Similar Documents

Stereospecific Cross-Coupling of Secondary Alkyl β-Trifluoroboratoamides

Stereospecific Synthesis and Characterization of Oligodeoxyribonucleotides Containing an N2 -(1-Carboxyethyl)-2′-deoxyguanosine

Toward β-Amino Acid Proteins: Design, Synthesis, and Characterization of a Fifteen Kilodalton β-Peptide Tetramer

Stereospecific decarboxylative allylation of sulfones

Cascade Reactions during Coronafacic Acid Biosynthesis: Elongation, Cyclization, and Functionalization during Cfa7-Catalyzed Condensation

Direct and Stereospecific Synthesis of Allenes via Reduction of Propargylic Alcohols with Cp2Zr(H)Cl

Tandem Action of the O2- and FADH2-Dependent Halogenases KtzQ and KtzR Produce 6,7-Dichlorotryptophan for Kutzneride Assembly

Halogenated β,γ-methylene- and ethylidene-dGTP-DNA ternary complexes with DNA polymerase β: structural evidence for stereospecific binding of the fluoromethylene analogues

Engineered Biosynthesis of Aklanonic Acid Analogs

Stereospecific Synthesis of threo- and erythro-β-Hydroxyglutamic Acid During Kutzneride Biosynthesis