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 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.

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 Manipulating Protein–Protein Interactions in Nonribosomal Peptide Synthetase Type II Peptidyl Carrier Proteins

Biochemistry ◽  
2017 ◽  
Vol 56 (40) ◽  
pp. 5269-5273 ◽  
Author(s):  
Matt J. Jaremko ◽  
D. John Lee ◽  
Ashay Patel ◽  
Victoria Winslow ◽  
Stanley J. Opella ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Nonribosomal Peptide Synthetase ◽  
Type Ii ◽  
Carrier Proteins ◽  
Protein Protein Interactions ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase

scholarly journals Draft Genome Sequence of Saccharomonospora sp. Strain LRS4.154, a Moderately Halophilic Actinobacterium with the Biotechnologically Relevant Polyketide Synthase and Nonribosomal Peptide Synthetase Systems

2017 ◽  
Vol 5 (21) ◽  
Author(s):  
Scarlett Alonso-Carmona ◽  
Blanca Vera-Gargallo ◽  
Rafael R. de la Haba ◽  
Antonio Ventosa ◽  
Horacio Sandoval-Trujillo ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Polyketide Synthase ◽  
Draft Genome ◽  
Nonribosomal Peptide Synthetase ◽  
Open Reading Frames ◽  
Draft Genome Sequence ◽  
Nonribosomal Peptide ◽  
Moderately Halophilic ◽  
Peptide Synthetase ◽  
Reading Frames

ABSTRACT The draft genome sequence of Saccharomonospora sp. strain LRS4.154, a moderately halophilic actinobacterium, has been determined. The genome has 4,860,108 bp, a G+C content of 71.0%, and 4,525 open reading frames (ORFs). The clusters of PKS and NRPS genes, responsible for the biosynthesis of a large number of biomolecules, were identified in the genome.

scholarly journals Total Biosynthesis and Diverse Applications of the Nonribosomal Peptide-Polyketide Siderophore Yersiniabactin

2015 ◽  
Vol 81 (16) ◽  
pp. 5290-5298 ◽  
Author(s):  
Mahmoud Kamal Ahmadi ◽  
Samar Fawaz ◽  
Charles H. Jones ◽  
Guojian Zhang ◽  
Blaine A. Pfeifer
Keyword(s):  
Polyketide Synthase ◽  
Parallel Applications ◽  
Total Removal ◽  
Heterologous Host ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Metal Chelating ◽  
Removal Capacity ◽  
Peptide Synthetase ◽  
Host Infection

ABSTRACTYersiniabactin (Ybt) is a mixed nonribosomal peptide-polyketide natural product natively produced by the pathogenYersinia pestis. The compound enables iron scavenging capabilities upon host infection and is biosynthesized by a nonribosomal peptide synthetase featuring a polyketide synthase module. This pathway has been engineered for expression and biosynthesis usingEscherichia colias a heterologous host. In the current work, the biosynthetic process for Ybt formation was improved through the incorporation of a dedicated step to eliminate the need for exogenous salicylate provision. When this improvement was made, the compound was tested in parallel applications that highlight the metal-chelating nature of the compound. In the first application, Ybt was assessed as a rust remover, demonstrating a capacity of ∼40% compared to a commercial removal agent and ∼20% relative to total removal capacity. The second application tested Ybt in removing copper from a variety of nonbiological and biological solution mixtures. Success across a variety of media indicates potential utility in diverse scenarios that include environmental and biomedical settings.

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

scholarly journals Polyketide Synthase and Nonribosomal Peptide Synthetase Gene Clusters in Type Strains of the Genus Phytohabitans

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 257
Author(s):  
Hisayuki Komaki ◽  
Tomohiko Tamura
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Nonribosomal Peptide Synthetase ◽  
Nrps Gene ◽  
Nonribosomal Peptide ◽  
Rare Actinomycetes ◽  
Whole Genomes ◽  
Peptide Synthetase ◽  
Established Genus

(1) Background: Phytohabitans is a recently established genus belonging to rare actinomycetes. It has been unclear if its members have the capacity to synthesize diverse secondary metabolites. Polyketide and nonribosomal peptide compounds are major secondary metabolites in actinomycetes and expected as a potential source for novel pharmaceuticals. (2) Methods: Whole genomes of Phytohabitans flavus NBRC 107702T, Phytohabitans rumicis NBRC 108638T, Phytohabitans houttuyneae NBRC 108639T, and Phytohabitans suffuscus NBRC 105367T were sequenced by PacBio. Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene clusters were bioinformatically analyzed in the genome sequences. (3) Results: These four strains harbored 10, 14, 18 and 14 PKS and NRPS gene clusters, respectively. Most of the gene clusters were annotated to synthesis unknown chemistries. (4) Conclusions: Members of the genus Phytohabitans are a possible source for novel and diverse polyketides and nonribosomal peptides.

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