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.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.