scholarly journals Conformational flexibility of coenzyme A and its impact on the post‐translational modification of acyl carrier proteins by 4′‐phosphopantetheinyl transferases

FEBS Journal ◽  
2020 ◽  
Vol 287 (21) ◽  
pp. 4729-4746
Author(s):  
Minh Chau Nguyen ◽  
Olivier Saurel ◽  
Coralie Carivenc ◽  
Sabine Gavalda ◽  
Stéphane Saitta ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Conformational Flexibility ◽  
Carrier Proteins ◽  
Post Translational Modification ◽  
Acyl Carrier Proteins ◽  
Phosphopantetheinyl Transferases

scholarly journals Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition

Science ◽  
2019 ◽  
Vol 363 (6426) ◽  
pp. eaau8959 ◽  
Author(s):  
Elaine Ballinger ◽  
John Mosior ◽  
Travis Hartman ◽  
Kristin Burns-Huang ◽  
Ben Gold ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Coenzyme A ◽  
Loss Of Function ◽  
Phosphopantetheinyl Transferase ◽  
Carrier Proteins ◽  
Regulatory Pathway ◽  
Acyl Carrier Proteins ◽  
Antimycobacterial Agents ◽  
Further Development ◽  
Cocrystal Structure

Mycobacterium tuberculosis (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb’s cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4′-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction. Thus, loss-of-function mutants of PptH displayed antimicrobial resistance. Our PptT-inhibitor cocrystal structure may aid further development of antimycobacterial agents against this long-sought target. The opposing reactions of PptT and PptH uncover a regulatory pathway in CoA physiology.

scholarly journals Improvement of Natamycin Production by Engineering of Phosphopantetheinyl Transferases in Streptomyces chattanoogensis L10

2013 ◽  
Vol 79 (11) ◽  
pp. 3346-3354 ◽  
Author(s):  
Hui Jiang ◽  
Yue-Yue Wang ◽  
Xin-Xin Ran ◽  
Wei-Ming Fan ◽  
Xin-Hang Jiang ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Type I ◽  
Type Ii ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins ◽  
Content Type ◽  
C Terminus ◽  
Spore Pigment ◽  
Phosphopantetheinyl Transferases ◽  
Streptomyces Chattanoogensis

ABSTRACTPhosphopantetheinyl transferases (PPTases) are essential to the activities of type I/II polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) through converting acyl carrier proteins (ACPs) in PKSs and peptidyl carrier proteins (PCPs) in NRPSs from inactive apo-forms into active holo-forms, leading to biosynthesis of polyketides and nonribosomal peptides. The industrial natamycin (NTM) producer,Streptomyces chattanoogensisL10, contains two PPTases (SchPPT and SchACPS) and five PKSs. Biochemical characterization of these two PPTases shows that SchPPT catalyzes the phosphopantetheinylation of ACPs in both type I PKSs and type II PKSs, SchACPS catalyzes the phosphopantetheinylation of ACPs in type II PKSs and fatty acid synthases (FASs), and the specificity of SchPPT is possibly controlled by its C terminus. Inactivation of SchPPT inS. chattanoogensisL10 abolished production of NTM but not the spore pigment, while overexpression of the SchPPT gene not only increased NTM production by about 40% but also accelerated productions of both NTM and the spore pigment. Thus, we elucidated a comprehensive phosphopantetheinylation network of PKSs and improved polyketide production by engineering the cognate PPTase in bacteria.

Post-translational modification of heterologously expressed Streptomyces type II polyketide synthase acyl carrier proteins

FEBS Letters ◽  
1997 ◽  
Vol 405 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Russell J Cox ◽  
Timothy S Hitchman ◽  
Kate J Byrom ◽  
I.Stuart C Findlow ◽  
Julian A Tanner ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Type Ii ◽  
Carrier Proteins ◽  
Post Translational Modification ◽  
Acyl Carrier Proteins

The substrate promiscuity of a phosphopantetheinyl transferase SchPPT for coenzyme A derivatives and acyl carrier proteins

2016 ◽  
Vol 198 (2) ◽  
pp. 193-197 ◽  
Author(s):  
Yue-Yue Wang ◽  
Hong-Dou Luo ◽  
Xiao-Sheng Zhang ◽  
Tao Lin ◽  
Hui Jiang ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Phosphopantetheinyl Transferase ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins ◽  
Substrate Promiscuity

scholarly journals Structure, function and dynamics in acyl carrier proteins

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0219435 ◽  
Author(s):  
Rohit Farmer ◽  
Christopher Morton Thomas ◽  
Peter James Winn
Keyword(s):  
Structure Function ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins

scholarly journals Genetic construction and functional analysis of hybrid polyketide synthases containing heterologous acyl carrier proteins.

1993 ◽  
Vol 175 (8) ◽  
pp. 2197-2204 ◽  
Author(s):  
C Khosla ◽  
R McDaniel ◽  
S Ebert-Khosla ◽  
R Torres ◽  
D H Sherman ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Polyketide Synthases ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins

scholarly journals The effect of divalent cations on the thermostability of type II polyketide synthase acyl carrier proteins

AIChE Journal ◽  
2018 ◽  
Vol 64 (12) ◽  
pp. 4308-4318 ◽  
Author(s):  
Marco A. Rivas ◽  
Valentine C. Courouble ◽  
Miranda C. Baker ◽  
David L. Cookmeyer ◽  
Kristen E. Fiore ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Divalent Cations ◽  
Type Ii ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins

scholarly journals Evolutionary significance of self-acylation property in acyl carrier proteins

IUBMB Life ◽  
2009 ◽  
Vol 61 (8) ◽  
pp. 853-859 ◽  
Author(s):  
Ashish Misra ◽  
Namita Surolia ◽  
Avadhesha Surolia
Keyword(s):  
Evolutionary Significance ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins
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