Recent advances in the structural analysis of adenylation domains in natural product biosynthesis |
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| Institution: | 1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India;2. National Institute of Immunology, New Delhi 110067, India;3. CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India;4. Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India;1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA;2. Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;3. Molecular Biology Section, Division of Biological Sciences, University of California San Diego, La Jolla, California, USA;4. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA;1. Hauptman-Woodward Medical Research Institute, Buffalo, NY, USA;2. Department of Structural Biology, University at Buffalo, Buffalo, NY, USA;1. Department of Biochemistry, McGill University, 3649 Promenade Sir William Osler, Francesco Bellini Life Sciences Building, Room 465, Montréal, QC H3G 0B1, Canada;1. Sauer Structural Biology Lab, The University of Texas at Austin, 102 E. 24th Street, Austin, TX 78712, USA;2. Department of Molecular Biosciences, The University of Texas at Austin, 100 E. 24th Street, Austin, TX 78712, USA;1. Department of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA;2. Joint Bioenergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA;3. QB3 Institute, University of California, Berkeley, Berkeley, CA 94270, USA;4. Department of Chemical and Biomolecular Engineering and Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA;5. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA |
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| Abstract: | Adenylation (A) domains catalyze the biosynthetic incorporation of acyl building blocks into nonribosomal peptides and related natural products by selectively transferring acyl substrates onto cognate carrier proteins (CP). The use of noncanonical acyl units, such as nonproteinogenic amino acids and keto acids, by A domains expands the structural diversity of natural products. Furthermore, interrupted A domains, which have embedded auxiliary domains, are able to modify the incorporated acyl units. Structural information on A domains is important for rational protein engineering to generate unnatural compounds. In this review, we summarize recent advances in the structural analysis of A domains. First, we discuss the mechanisms by which A domains recognize noncanonical acyl units. We then focus on the interactions of A domains with CP domains and embedded auxiliary domains. |
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| Keywords: | Biosynthesis Natural product Nonribosomal peptide synthetase Protein–protein interaction |
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