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Literature DB >> 28218912

Engineering fatty acid synthases for directed polyketide production.

Jan Gajewski¹, Floris Buelens², Sascha Serdjukow³, Melanie Janßen¹, Niña Cortina¹, Helmut Grubmüller², Martin Grininger^1,3.

Abstract

In this study, we engineered fatty acid synthases (FAS) for the biosynthesis of short-chain fatty acids and polyketides, guided by a combined in vitro and in silico approach. Along with exploring the synthetic capability of FAS, we aim to build a foundation for efficient protein engineering, with the specific goal of harnessing evolutionarily related megadalton-scale polyketide synthases (PKS) for the tailored production of bioactive natural compounds.

Entities: Chemical

Mesh：

Substances：

Year: 2017 PMID： 28218912 DOI： 10.1038/nchembio.2314

Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040

29 in total

1. Development and testing of a general amber force field.

Authors: Junmei Wang; Romain M Wolf; James W Caldwell; Peter A Kollman; David A Case
Journal: J Comput Chem Date: 2004-07-15 Impact factor: 3.376

2. Linear-scaling soft-core scheme for alchemical free energy calculations.

Authors: Floris P Buelens; Helmut Grubmüller
Journal: J Comput Chem Date: 2011-09-26 Impact factor: 3.376

3. Microbial engineering for the production of advanced biofuels.

Authors: Pamela P Peralta-Yahya; Fuzhong Zhang; Stephen B del Cardayre; Jay D Keasling
Journal: Nature Date: 2012-08-16 Impact factor: 49.962

4. Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery.

Authors: J G Olsen; A Kadziola; P von Wettstein-Knowles; M Siggaard-Andersen; S Larsen
Journal: Structure Date: 2001-03-07 Impact factor: 5.006

5. Reaction of yeast fatty acid synthetase with iodoacetamide. 3. Malonyl-coenzyme A decarboxylase as product of the reaction of fatty acid synthetase with iodoacetamide.

Authors: G B Kresze; L Steber; D Oesterhelt; F Lynen
Journal: Eur J Biochem Date: 1977-09-15

Review 6. Structure and mechanism of assembly line polyketide synthases.

Authors: Thomas Robbins; Yu-Chen Liu; David E Cane; Chaitan Khosla
Journal: Curr Opin Struct Biol Date: 2016-06-05 Impact factor: 6.809

7. Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.

Authors: Gabor Bunkoczi; Stephanie Misquitta; Xiaoqiu Wu; Wen Hwa Lee; Alexandra Rojkova; Grazyna Kochan; Kathryn L Kavanagh; Udo Oppermann; Stuart Smith
Journal: Chem Biol Date: 2009-06-26

8. Improved side-chain torsion potentials for the Amber ff99SB protein force field.

Authors: Kresten Lindorff-Larsen; Stefano Piana; Kim Palmo; Paul Maragakis; John L Klepeis; Ron O Dror; David E Shaw
Journal: Proteins Date: 2010-06

9. Towards computational specificity screening of DNA-binding proteins.

Authors: Daniel Seeliger; Floris P Buelens; Maik Goette; Bert L de Groot; Helmut Grubmüller
Journal: Nucleic Acids Res Date: 2011-07-06 Impact factor: 16.971

10. Crystallization and X-ray diffraction studies of a complete bacterial fatty-acid synthase type I.

Authors: Mathias Enderle; Andrew McCarthy; Karthik Shivaji Paithankar; Martin Grininger
Journal: Acta Crystallogr F Struct Biol Commun Date: 2015-10-23 Impact factor: 1.056

20 in total

1. Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I.

Authors: Alexander Rittner; Karthik S Paithankar; David Jan Drexler; Aaron Himmler; Martin Grininger
Journal: Protein Sci Date: 2018-12-20 Impact factor: 6.725

2. Fatty acid synthases: Re-engineering biofactories.

Authors: Timm Maier
Journal: Nat Chem Biol Date: 2017-03-22 Impact factor: 15.040

3. Computational structural enzymology methodologies for the study and engineering of fatty acid synthases, polyketide synthases and nonribosomal peptide synthetases.

Authors: Andrew J Schaub; Gabriel O Moreno; Shiji Zhao; Hau V Truong; Ray Luo; Shiou-Chuan Tsai
Journal: Methods Enzymol Date: 2019-04-22 Impact factor: 1.600

Engineering fatty acid synthases for directed polyketide production.

1. Development and testing of a general amber force field.

2. Linear-scaling soft-core scheme for alchemical free energy calculations.

3. Microbial engineering for the production of advanced biofuels.

4. Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery.

5. Reaction of yeast fatty acid synthetase with iodoacetamide. 3. Malonyl-coenzyme A decarboxylase as product of the reaction of fatty acid synthetase with iodoacetamide.

Review 6. Structure and mechanism of assembly line polyketide synthases.

7. Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.

8. Improved side-chain torsion potentials for the Amber ff99SB protein force field.

9. Towards computational specificity screening of DNA-binding proteins.

10. Crystallization and X-ray diffraction studies of a complete bacterial fatty-acid synthase type I.

1. Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I.

2. Fatty acid synthases: Re-engineering biofactories.

3. Computational structural enzymology methodologies for the study and engineering of fatty acid synthases, polyketide synthases and nonribosomal peptide synthetases.

Review 4. The architectures of iterative type I PKS and FAS.

5. Expanding the product portfolio of fungal type I fatty acid synthases.

6. Molecular basis for interactions between an acyl carrier protein and a ketosynthase.

Review 7. Microbial synthesis of medium-chain chemicals from renewables.

8. Production of pikromycin using branched chain amino acid catabolism in Streptomyces venezuelae ATCC 15439.

9. Interfacial plasticity facilitates high reaction rate of E. coli FAS malonyl-CoA:ACP transacylase, FabD.

10. Structural insight into Pichia pastoris fatty acid synthase.