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Fatty Acyl-AMP Ligases as Mechanistic Variants of ANL Superfamily and Molecular Determinants Dictating Substrate Specificities

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Journal of the Indian Institute of Science Aims and scope

Abstract

Fatty acyl-AMP ligases (FAAL) are enzymes that establish the crosstalk between fatty acid synthases and polyketide synthases or non-ribosomal peptide synthetases by activating newly synthesized fatty acids, shuttling them towards polyketide synthesis. These enzymes are unique as they have evolved a strict rejection mechanism for the coenzyme-A but can recognize and react with the phosphopantetheine of acyl-carrier proteins. A strategically placed insertion in the N-terminal domain and the rigidity of the hydrophobic anchor holding the insertion is at the heart of such a discrimination mechanism, the molecular details of which is yet to be clearly understood. The unique structural features of the insertion have been exploited to filter out FAALs from other members of the superfamily, in silico. Interestingly, several independent studies have characterized FAALs from different organisms such as Legionella, Myxococcus, Ralstonia, Pseudoalteromonas, Sorangium, etc. to name a few, laying emphasis on the usage of a FAAL-specific biochemistry in these organisms, particularly for the production of important bioactive molecules. These bioactive molecules help in improving the fitness of these systems to tide over the competition for nutritional resources in their local niche. Substrate specificity of these enzymes is another interesting aspect, which may hint at their potential roles in the cell. Various substrate-bound crystal structures have been used to identify the determinants of chain-length specificity and predict the preferences for different FAALs (both mycobacterial and non-mycobacterial). The fascinating details of the mechanistic variation of these enzymes and the molecular determinants that define the chain-length specificity have been discussed herewith.

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Acknowledgements

R. S. acknowledges funding from JC Bose Fellowship of Science and Engineering Research Board (SERB), India, and Centre of Excellence Project of Department of Biotechnology, India.

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  1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

    Kinatukara Priyadarshan & Rajan Sankaranarayanan

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  1. Kinatukara Priyadarshan
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  2. Rajan Sankaranarayanan
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Correspondence to Rajan Sankaranarayanan.

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Priyadarshan, K., Sankaranarayanan, R. Fatty Acyl-AMP Ligases as Mechanistic Variants of ANL Superfamily and Molecular Determinants Dictating Substrate Specificities. J Indian Inst Sci 98, 261–272 (2018). https://doi.org/10.1007/s41745-018-0084-2

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  • DOI: https://doi.org/10.1007/s41745-018-0084-2

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