Insights into modular polyketide synthase loops aided by repetitive sequences

The loops of modular polyketide synthases (PKSs) serve diverse functions but are largely uncharacterized. They frequently contain amino acid repeats resulting from genetic events such as slipped‐strand mispairing. Determining the tolerance of loops to amino acid changes would aid in understanding an...

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Published in:Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2021-09, Vol.89 (9), p.1099-1110
Main Authors: Hirsch, Melissa, Kumru, Kaan, Desai, Ronak R., Fitzgerald, Brendan J., Miyazawa, Takeshi, Ray, Katherine A., Saif, Nisha, Spears, Samantha, Keatinge‐Clay, Adrian T.
Format: Article
Language:English
Subjects:
Acyl Carrier Protein - chemistry
Acyl Carrier Protein - classification
Acyl Carrier Protein - genetics
Acyl Carrier Protein - metabolism
Acyltransferase
Acyltransferases - chemistry
Acyltransferases - classification
Acyltransferases - genetics
Acyltransferases - metabolism
Amino Acid Sequence
Amino acids
Bacteria - enzymology
Bacteria - genetics
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Binding Sites
biosynthesis
Cloning, Molecular
Crystallography, X-Ray
Dehydration
Deoxyribonucleic acid
DNA
Escherichia coli - genetics
Escherichia coli - metabolism
Gene Expression
Genetic Vectors - chemistry
Genetic Vectors - metabolism
Industrial engineering
Kinetics
loops
Manufacturing engineering
Models, Molecular
modular polyketide synthase
Modules
multidomain protein
Polyketide synthase
Polyketide Synthases - chemistry
Polyketide Synthases - classification
Polyketide Synthases - genetics
Polyketide Synthases - metabolism
Polyketides - chemistry
Polyketides - metabolism
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
repetitive sequences
Sequence Alignment
Sequence Homology, Amino Acid
Substrate Specificity
Thermodynamics
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Summary:The loops of modular polyketide synthases (PKSs) serve diverse functions but are largely uncharacterized. They frequently contain amino acid repeats resulting from genetic events such as slipped‐strand mispairing. Determining the tolerance of loops to amino acid changes would aid in understanding and engineering these multidomain molecule factories. Here, tandem repeats in the DNA encoding 949 modules within 129 cis‐acyltransferase PKSs were cataloged, and the locations of the corresponding amino acids within the module were identified. The most frequently inserted interdomain loop corresponds with the updated module boundary immediately downstream of the ketosynthase (KS), while the loops bordering the dehydratase are nearly intolerant to such insertions. From the 949 modules, no repetitive sequence loop insertions are located within ACP, and only 2 reside within KS, indicating the sensitivity of these domains to alteration.
ISSN:0887-3585
1097-0134
DOI:10.1002/prot.26083