The l ‐Alanosine Gene Cluster Encodes a Pathway for Diazeniumdiolate Biosynthesis
| Autor: | Christine R. Zheng, Tai L. Ng, Kelvin J. Y. Wu, Monica E. McCallum, Jennifer X. Wang, Emily P. Balskus |
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| Rok vydání: | 2019 |
| Předmět: |
010402 general chemistry
01 natural sciences Biochemistry Article chemistry.chemical_compound Bacterial Proteins Biosynthesis Gene cluster Structural motif Molecular Biology Gene chemistry.chemical_classification Alanine Natural product Molecular Structure 010405 organic chemistry Organic Chemistry Streptomyces Biosynthetic Pathways 0104 chemical sciences 3. Good health Streptomyces alanosinicus Amino acid Enzyme chemistry Multigene Family Molecular Medicine Azo Compounds |
| Zdroj: | Chembiochem |
| ISSN: | 1439-7633 1439-4227 |
| DOI: | 10.1002/cbic.201900565 |
| Popis: | N-Nitroso-containing natural products are bioactive metabolites with antibacterial and anticancer properties. In particular, compounds containing the diazeniumdiolate (N-nitrosohydroxylamine) group display a wide range of bioactivities ranging from cytotoxicity to metal chelation. Despite the importance of this structural motif, knowledge of its biosynthesis is limited. Herein we describe the discovery of a biosynthetic gene cluster in Streptomyces alanosinicus ATCC 15710 responsible for producing the diazeniumdiolate natural product l-alanosine. Gene disruption and stable isotope feeding experiments identified essential biosynthetic genes and revealed the source of the N-nitroso group. Additional biochemical characterization of the biosynthetic enzymes revealed that the non-proteinogenic amino acid l-2,3-diaminopropionic acid (l-Dap) is synthesized and loaded onto a free-standing peptidyl carrier protein (PCP) domain in l-alanosine biosynthesis, which we propose may be a mechanism of handling unstable intermediates generated en route to the diazeniumdiolate. These discoveries will facilitate efforts to determine the biochemistry of diazeniumdiolate formation. |
| Databáze: | OpenAIRE |
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