開催日: 2017/09/20 - 2017/09/22
Fungal polyketides, synthesized by iterative polyketide synthases (IPKSs), comprise a structurally diverse family of natural products, displaying a wide range of biological activities. Nature can increase the structural diversity of polyketides by collaboratively pairing IPKSs in the same biosynthetic pathway. Collaborative IPKSs are frequently colocalized in the same biosynthetic gene cluster, a genetic feature that can be utilized in the genome mining of new natural products. One strategy to install nitrogen-containing functional groups in fungal polyketides is through the action of hybrid megasynthases known as PKS-NRPSs. The cis-acting NRPS module can amidate the completed polyketide acyl chain with a specific amino acid selected by the adenylation domain. The aminoacyl polyketide can then be cyclized into compounds that contain a nitrogen heterocycle, such as tetramate. Hence, one would expect pairing a PKS-NRPS with other IPKSs can lead to additional structural diversity. Here we demonstrate a new mode of collaboration between an HRPKS and a PKS-NRPS, in which the HRPKS is responsible for the biosynthesis of free, unnatural amino acid that is subsequently incorporated by the PKS-NRPS to generate new succinimide and maleimide containing natural products.