Mechanism Studies on Fungal Type I Highly-Reducing Polyketide Synthases and Polyketide Synthase-Nonribosomal Peptide Synthetase Hybrids
作者： Wei Xu
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摘要: Filamentous fungi are known as promising sources for bio-active natural products, some of which blockbuster drugs, such penicillin and lovastatin. Fungal polyketide synthases (PKSs) nonribosomal peptide synthetases (NRPSs) large highly complex multidomain megasynthetases with programming rules. Different from their well-studied bacterial counterparts, the mechanisms these megasynthases not well understood to date. The thesis focuses on mechanism study two fungal reducing PKSs involved in lovastatin biosynthesis a PKS-NRPS hybrid Apsergillus sp.Using developed expression system S. cerevisiae, we were able probe property enzymes under different conditions vivo experiment heterologous host vitro assays. In project, observed studied interaction between highly-reducing synthase (HR-PKS) its product releasing partner. These PKS/releasing-enzyme pairs could widely exist HR-PKS systems. It also shows applications drug industry because efficiency directly determine yield products. related hybrid, be first group reconstitute full function this type megasynthetase both PKS NRPS module hybrid. More importantly, modules.
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