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Full-Text Articles in Biomedical Engineering and Bioengineering
New Insights Into The Glycosylation Steps In The Biosynthesis Of Sch47554 And Sch47555, Ozkan Fidan, Riming Yan, Gabrielle Gladstone, Tong Zhou, Du Zhu, Jixun Zhan
New Insights Into The Glycosylation Steps In The Biosynthesis Of Sch47554 And Sch47555, Ozkan Fidan, Riming Yan, Gabrielle Gladstone, Tong Zhou, Du Zhu, Jixun Zhan
Biological Engineering Faculty Publications
Sch47554 and Sch47555 are antifungal compounds from Streptomyces sp. SCC‐2136. The availability of the biosynthetic gene cluster made it possible to track genes that encode biosynthetic enzymes responsible for the structural features of these two angucyclines. Sugar moieties play important roles in the biological activities of many natural products. An investigation into glycosyltransferases (GTs) might potentially help to diversify pharmaceutically significant drugs through combinatorial biosynthesis. Sequence analysis indicates that SchS7 is a putative C‐GT, whereas SchS9 and SchS10 are proposed to be O‐GTs. In this study, the roles of these three GTs in the biosynthesis of Sch47554 and Sch47555 are …
Decoding And Reprogramming Fungal Iterative Nonribosomal Peptide Synthetases, Daya Yu, Fuchao Xu, Shuwei Zhang, Jixun Zhan
Decoding And Reprogramming Fungal Iterative Nonribosomal Peptide Synthetases, Daya Yu, Fuchao Xu, Shuwei Zhang, Jixun Zhan
Biological Engineering Faculty Publications
Nonribosomal peptide synthetases (NRPSs) assemble a large group of structurally and functionally diverse natural products. While the iterative catalytic mechanism of bacterial NRPSs is known, it remains unclear how fungal NRPSs create products of desired length. Here we show that fungal iterative NRPSs adopt an alternate incorporation strategy. Beauvericin and bassianolide synthetases have the same C1-A1-T1-C2-A2-MT-T2a-T2b-C3 domain organization. During catalysis, C3 and C2 take turns to incorporate the two biosynthetic precursors into the growing depsipeptide chain that swings between T1 and T …
Rational Reprogramming Of Fungal Polyketide First Ring Cyclization, Yuquan Xu, Tong Zhou, Zhengfu Zhou, Shiyou Su, Sue A. Roberts, William R. Montfort, Jia Zeng, Ming Chen, Wei Zhang, Min Lin, Jixun Zhan, Istvan Molnar
Rational Reprogramming Of Fungal Polyketide First Ring Cyclization, Yuquan Xu, Tong Zhou, Zhengfu Zhou, Shiyou Su, Sue A. Roberts, William R. Montfort, Jia Zeng, Ming Chen, Wei Zhang, Min Lin, Jixun Zhan, Istvan Molnar
Biological Engineering Faculty Publications
Resorcylic acid lactones (RAL) and dihydroxyphenylacetic acid lactones (DAL) represent important pharmacophores with heat shock response and immune system modulatory activities. The biosynthesis of these fungal polyketides involves a pair of collaborating iterative polyketide synthases (iPKSs): a highly reducing iPKS (hrPKS) whose product is further elaborated by a nonreducing iPKS (nrPKS) to yield a 1,3-benzenediol moiety bridged by a macrolactone. Biosynthesis of unreduced polyketides requires the sequestration and programmed cyclization of highly reactive poly-β-ketoacyl intermediates to channel these uncommitted, pluripotent substrates towards defined subsets of the polyketide structural space. Catalyzed by product template (PT) domains of the fungal nrPKSs and …