Loading of malonyl-CoA onto tandem acyl carrier protein domains of polyunsaturated fatty acid synthases

• Published in: The Journal of biological chemistry Vol. 293; no. 32; pp. 12491 - 12501
• Main Authors: Santín, Omar, Moncalián, Gabriel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2018; American Society for Biochemistry and Molecular Biology
• Subjects: acyl carrier protein (ACP); Acyl Carrier Protein - chemistry; Acyl Carrier Protein - metabolism; acyltransferase; Amino Acid Sequence; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Enzymology; fatty acid synthase (FAS); Fatty Acid Synthases - chemistry; Fatty Acid Synthases - metabolism; Fatty Acids, Unsaturated - metabolism; Flavobacteriaceae - metabolism; Malonyl Coenzyme A - metabolism; polyketide; polyunsaturated fatty acid (PUFA); Protein Conformation; Protein Domains; Sequence Homology; fatty acid synthase (FAS); acyl carrier protein (ACP); polyketide; polyunsaturated fatty acid (PUFA); acyltransferase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA118.002443

Omega-3 polyunsaturated fatty acids (PUFA) are produced in some unicellular organisms, such as marine gammaproteobacteria, myxobacteria, and thraustochytrids, by large enzyme complexes called PUFA synthases. These enzymatic complexes resemble bacterial antibiotic-producing proteins known as polyketide synthases (PKS). One of the PUFA synthase subunits is a conserved large protein (PfaA in marine proteobacteria) that contains three to nine tandem acyl carrier protein (ACP) domains as well as condensation and modification domains. In this work, a study of the PfaA architecture and its ability to initiate the synthesis by selecting malonyl units has been carried out. As a result, we have observed a self-acylation ability in tandem ACPs whose biochemical mechanism differ from the previously described for type II PKS. The acyltransferase domain of PfaA showed a high selectivity for malonyl-CoA that efficiently loads onto the ACPs domains. These results, together with the structural organization predicted for PfaA, suggest that this protein plays a key role at early stages of the anaerobic pathway of PUFA synthesis.