Selective Protein−Protein Interactions Direct Channeling of Intermediates between Polyketide Synthase Modules†

Biochemistry ◽  
2001 ◽  
Vol 40 (8) ◽  
pp. 2326-2331 ◽  
Author(s):  
Stuart Y. Tsuji ◽  
David E. Cane ◽  
Chaitan Khosla
Keyword(s):  
Protein Interactions ◽  
Polyketide Synthase ◽  
Protein Protein Interactions

scholarly journals Probing the Selectivity and Protein⋅Protein Interactions of a Nonreducing Fungal Polyketide Synthase Using Mechanism-Based Crosslinkers

2014 ◽  
Vol 21 (7) ◽  
pp. 913
Author(s):  
Joel Bruegger ◽  
Robert W. Haushalter ◽  
Anna L. Vagstad ◽  
Joris Beld ◽  
Gaurav Shakya ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Polyketide Synthase ◽  
Protein Protein Interactions

Protein–protein interactions in polyketide synthase–nonribosomal peptide synthetase hybrid assembly lines

2018 ◽  
Vol 35 (11) ◽  
pp. 1185-1209 ◽  
Author(s):  
Akimasa Miyanaga ◽  
Fumitaka Kudo ◽  
Tadashi Eguchi
Keyword(s):  
Protein Interactions ◽  
Polyketide Synthase ◽  
Nonribosomal Peptide Synthetase ◽  
Hybrid Assembly ◽  
Protein Protein Interactions ◽  
Assembly Lines ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase

The protein–protein interactions in polyketide synthase–nonribosomal peptide synthetase hybrids are summarized and discussed.

scholarly journals Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Likui Feng ◽  
Matthew T. Gordon ◽  
Ying Liu ◽  
Kari B. Basso ◽  
Rebecca A. Butcher
Keyword(s):  
Protein Interactions ◽  
Biosynthetic Pathway ◽  
Polyketide Synthase ◽  
Carrier Protein ◽  
Nonribosomal Peptides ◽  
Direct Transfer ◽  
Protein Protein Interactions ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase ◽  
Complex Protein

AbstractPolyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between these multimodular megaenzymes. In the canal-associated neurons (CANs) of Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides biosynthesized by animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry to map the roles of individual PKS-1 and NRPS-1 enzymatic domains in nemamide biosynthesis. Furthermore, we show that nemamide biosynthesis requires at least five additional enzymes expressed in the CANs that are encoded by genes distributed across the worm genome. We identify the roles of these enzymes and discover a mechanism for trafficking intermediates between a PKS and an NRPS. Specifically, the enzyme PKAL-1 activates an advanced polyketide intermediate as an adenylate and directly loads it onto a carrier protein in NRPS-1. This trafficking mechanism provides a means by which a PKS-NRPS system can expand its biosynthetic potential and is likely important for the regulation of nemamide biosynthesis.

scholarly journals Engineering strategies for rational polyketide synthase design

2018 ◽  
Vol 35 (10) ◽  
pp. 1070-1081 ◽  
Author(s):  
Maja Klaus ◽  
Martin Grininger
Keyword(s):  
Protein Interactions ◽  
Assembly Line ◽  
Polyketide Synthase ◽  
Polyketide Synthases ◽  
Protein Protein Interactions ◽  
Important Protein ◽  
Line P

In this review, we highlight strategies in engineering polyketide synthases (PKSs). We focus on important protein–protein interactions that constitute an intact PKS assembly line.

scholarly journals Probing the Selectivity and Protein⋅Protein Interactions of a Nonreducing Fungal Polyketide Synthase Using Mechanism-Based Crosslinkers

2013 ◽  
Vol 20 (9) ◽  
pp. 1135-1146 ◽  
Author(s):  
Joel Bruegger ◽  
Bob Haushalter ◽  
Anna Vagstad ◽  
Gaurav Shakya ◽  
Nathan Mih ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Polyketide Synthase ◽  
Protein Protein Interactions

scholarly journals Mapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan

2021 ◽  
Author(s):  
Likui Feng ◽  
Matthew T. Gordon ◽  
Ying Liu ◽  
Kari B. Basso ◽  
Rebecca A. Butcher
Keyword(s):  
Protein Interactions ◽  
Biosynthetic Pathway ◽  
Polyketide Synthase ◽  
Carrier Protein ◽  
Direct Transfer ◽  
Protein Protein Interactions ◽  
Nematode Caenorhabditis Elegans ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase ◽  
Complex Protein

Hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between megasynthases. In the nematode Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides in animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry to map the roles of individual PKS-1 and NRPS-1 enzymatic domains in nemamide biosynthesis. Furthermore, we show that nemamide biosynthesis requires at least five additional stand-alone enzymes that are encoded by genes distributed across the worm genome. We identify the roles of these enzymes in the biosynthetic pathway and discover a novel mechanism of trafficking intermediates between a PKS and an NRPS. Specifically, we show that the enzyme PKAL-1 activates an advanced polyketide intermediate as an adenylate and directly loads it onto a carrier protein in NRPS-1. This trafficking provides a means by which a PKS-NRPS system can expand its biosynthetic potential and is likely important for the regulation of nemamide biosynthesis.

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