De Novo Design and Implementation of a Tandem Acyl Carrier Protein Domain in a Type I Modular Polyketide Synthase
| Autor: | Zilong Wang, Chu-Young Kim, Gerardo Zavala, Xi Chen, Saket R. Bagde, Tsutomu Matsui |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Fatty acid biosynthesis Stereochemistry Protein Engineering 010402 general chemistry Thioester 01 natural sciences Biochemistry Article 03 medical and health sciences Polyketide Protein Domains Polyketide synthase Acyl Carrier Protein Escherichia coli Amino Acid Sequence chemistry.chemical_classification biology Tandem General Medicine 0104 chemical sciences Kinetics Acyl carrier protein 030104 developmental biology Enzyme chemistry Polyketides Acyl chain biology.protein Molecular Medicine lipids (amino acids peptides and proteins) Polyketide Synthases Saccharopolyspora |
| Zdroj: | ACS Chemical Biology. 13:3072-3077 |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | During polyketide and fatty acid biosynthesis, the growing acyl chain is attached to the acyl carrier protein via a thioester linkage. The acyl carrier protein interacts with other enzymes that perform chain elongation and chain modification on the bound acyl chain. Most type I polyketide synthases and fatty acid synthases contain only one acyl carrier protein. However, polyunsaturated fatty acid synthases from deep-sea bacteria contain anywhere from two to nine acyl carrier proteins. Recent studies have shown that this tandem acyl carrier protein feature is responsible for the unusually high fatty acid production rate of deep-sea bacteria. To investigate if a similar strategy can be used to increase the production rate of type I polyketide synthases, a 3×ACP domain was rationally designed and genetically installed in module 6 of 6-deoxyerythronolide B synthase, which is a prototypical type I modular polyketide synthase that naturally harbors just one acyl carrier protein. This modification resulted in an ~2.5-fold increase in the total amount of polyketide produced in vitro, demonstrating that installing a tandem acyl carrier domain in a type I polyketide synthase is an effective strategy for enhancing the rate of polyketide natural product biosynthesis. |
| Databáze: | OpenAIRE |
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