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Structure of a ketosynthase-chain length factor of a polyunsaturated fatty acids synthase
|Authors:||Santín, Omar; Moncalián, Gabriel CSIC ORCID||Issue Date:||2016||Citation:||ICCBM-16 (2016)||Abstract:||The use of omega-3 polyunsaturated fatty acids (O3PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has increased in recent years because of its benefits for human health. . For the production of these O3PUFAs, marine bacteria such as moritella marina or colwellia psychrerythraea (DHA producers) or Shewanella baltica (EPA producer) possess large enzyme complexes called PUFA synthases (Pfa), which resemble bacterial antibiotic production proteins known as polyketide synthases (PKS). For growing PUFA carbon chain, some essential enzyme modules are needed to produce the first decarboxylation and successive condensations rounds. These modules consist of heterodimers of keto synthases (KS) and acyltransferase (AT) that, in coordination with acyl carrier proteins (ACPs), incorporate acyl groups to the growing chain, performing the so-called claisen condensations. In cases where long-chain PUFAs are synthesized, the chain elongation is guided by a special heterodimeric Ketosynthase-Chain length factor (KS-CLF) domain. In contrast to homodimeric KS-KS domains found in regular fatty acid synthases, the active site cysteine is absent from the C-terminal subunit of this KS-CLF heterodimer. A hydrophobic tunnel that holds the growing chain is a critical determinant of the final polyketide chain length. Besides determining the final length of PUFAs, KS-CLF heterodimer can decarboxylate malonyl units, thus >seeding> the acyl chain in the first cyclization of the polyketide and placing the new molecule within the KS-CLF tunnel. We have recently obtained crystals of a 100 kDa Ketosynthase-Chain length factor heterodimer from a PUFA synthase. These crystals were diffracted at ALBA synchrotron in Barcelona (Spain) and the protein structure was solved by molecular replacement at 1.9 A resolution. This first solved structure of a Pfa KS-CLF heterodimer resulted to be very informative to understand the role of this domain in O3PUFA synthesis. Moreover, biochemical studies in combination with modeling of the other Pfa modules allowed us to propose a model of the overall Pfa architecture. These structural studies could be used for the modification and optimization of O3PUFA synthesis in different microorganisms.||Description:||Resumen del póster presentado a la 16th International Conference on the Crystallization of Biological Macromolecules, celebrada en Praga (República Checa) del 2 al 7 de julio de 2016.||URI:||http://hdl.handle.net/10261/164799|
|Appears in Collections:||(IBBTEC) Comunicaciones congresos|
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