A hybrid assembly mechanism employs nonreducing polyketide synthase-like logic for partially reduced polyketide formationOA
Fungal iterative type I polyketide synthases(iPKSs)are commonly classified into nonreducing(NR-),partially reducing(PR-),and highly reducing(HR-)polyketide synthases based on their assembly mechanisms and domain structures.These iPKSs have been considered functionally and evolutionarily distinct,characterized by clear boundaries.However,emerging genomic analyses suggest that the diversity of iPKSs in fungi is far from fully understood.Here,we describe the discovery and characterization of PbPKS1 from a marine-derived fungus Penicillium brocae HDN12-143,which exhibits an atypical domain organization arranged as KR-KS-AT-PT-ACP1-ACP2-CMeT-TE.Heterologous expression of PbPKS1 resulted in the production of two monohydroxybenzoic acids and two pyrones.In vivo and in vitro characterizations demonstrated that PbPKS1 has the capability to synthesize Cα-methylated partially reducing polyketides,yet involved a NR-PKS-like assembly mechanism,featuring a product template(PT)domain for aldol cyclization and a C-terminal thioesterase(TE)domain for product release.Phylogenetic analysis suggests that PbPKS1 belongs to a non-canonical PR-PKS(nPR-PKS)family,which is a minor grouping across the fungal kingdom,and possibly evolved from an NR-PKS through gene recombination.The discovery of nPR-PKS not only expands the diversity of iPKSs but also provides new insights into the evolutionary development of fungal iPKSs.
Xianyan Zhang;Chuanteng Ma;Ziguang Deng;Xingtao Ren;Kaijin Zhang;Wenxue Wang;Luning Zhou;Yongchun Zhu;Guojian Zhang;Qian Che;Tianjiao Zhu;Hongan Long;Bo Dong;Dehai Li
Key Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,China Key Laboratory of Evolution&Marine Biodiversity Ministry of Education,Institute of Evolution&Marine Biodiversity,College of Marine Life Science,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Evolution&Marine Biodiversity Ministry of Education,Institute of Evolution&Marine Biodiversity,College of Marine Life Science,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Evolution&Marine Biodiversity Ministry of Education,Institute of Evolution&Marine Biodiversity,College of Marine Life Science,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Evolution&Marine Biodiversity Ministry of Education,Institute of Evolution&Marine Biodiversity,College of Marine Life Science,Ocean University of China,Qingdao,266003,ChinaKey Laboratory of Marine Drugs Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao,266003,China Sanya Oceanographic Institute,Ocean University of China,Sanya,572024,China Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center,Qingdao,266237,China
生物科学
Iterative polyketide synthases(iPKSs)Product templateNonreducing PKS(NR-PKS)Partially reducing PKS(PR-PKS)Domain recombination
《Marine Life Science & Technology》 2026 (1)
P.180-191,12
supported by Qingdao Marine Science and Technology Center(2022QNLM030003-1)the Fundamental Research Funds for the Central Universities(202172002,202262015)National Key R&D Program of China(2022YFC2807502).
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