1. Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis.
- Author
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Smanski MJ, Yu Z, Casper J, Lin S, Peterson RM, Chen Y, Wendt-Pienkowski E, Rajski SR, and Shen B
- Subjects
- Adamantane metabolism, Aminobenzoates metabolism, Aminophenols metabolism, Anilides metabolism, Anti-Bacterial Agents, Hypoglycemic Agents, Metabolic Networks and Pathways, Molecular Sequence Data, Polycyclic Compounds metabolism, Streptomyces metabolism, Adamantane chemical synthesis, Alkyl and Aryl Transferases metabolism, Aminobenzoates chemical synthesis, Aminophenols chemical synthesis, Anilides chemical synthesis, Polycyclic Compounds chemical synthesis, Streptomyces enzymology
- Abstract
Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases and have emerged as promising drug leads for both antibacterial and antidiabetic therapies. Comparative analysis of the PTM and PTN biosynthetic machineries in Streptomyces platensis MA7327 and MA7339 revealed that the divergence of PTM and PTN biosynthesis is controlled by dedicated ent-kaurene and ent-atiserene synthases, the latter of which represents a new pathway for diterpenoid biosynthesis. The PTM and PTN biosynthetic machineries provide a rare glimpse at how secondary metabolic pathway evolution increases natural product structural diversity and support the wisdom of applying combinatorial biosynthesis methods for the generation of novel PTM and/or PTN analogues, thereby facilitating drug development efforts based on these privileged natural product scaffolds.
- Published
- 2011
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