According to reports, PTM compounds are a class of natural products that are widely present and diverse in activity. Its structure is complex, with a polycyclic fused macrocyclic lactam structure, belonging to polyketone and non-ribosomal peptide hybrid antibiotics. Although scientists have discovered the PTMs gene cluster and speculated that the polyketide synthase/non-ribosomal peptide synthetase assembles the source nature of the PTM compound skeleton, the polycyclic formation mechanism of PTMs compounds remains an unsolved mystery.
Cantharidin is a representative compound of the PTMs family, and its unique structure and excellent anti-tumor activity have attracted wide attention. The researchers discovered cantharidin from Streptomyces sp. ZJ306, a sediment source from the Pearl River Estuary, and found that the biosynthesis of cantharidin is derived from polyketide synthase and non-ribosomal peptides, consistent with other PTMs compounds. Hybrid pathway for synthetase (PKS/NRPS).
Through gene knockout and heterologous expression techniques, the scientists determined that the three genes ikaABC are sufficient to mediate the heterologous biosynthesis of cantharidin, and at the same time preliminarily clarify the function and reaction sequence of ikaABC. This unique reductive cyclization mechanism was resolved and confirmed by in vitro biochemical and ingenious helium atomic labeling experiments.
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