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Literature DB >> 33857369

Targeted Genome Mining Reveals the Biosynthetic Gene Clusters of Natural Product CYP51 Inhibitors.

Nicholas Liu, Elizabeth D Abramyan, Wei Cheng, Bruno Perlatti¹, Colin J B Harvey², Gerald F Bills¹, Yi Tang.

Abstract

Lanosterol 14α-demethylase (CYP51) is an important target in the development of antifungal drugs. The fungal-derived restricticin 1 and related molecules are the only examples of natural products that inhibit CYP51. Here, using colocalizations of genes encoding self-resistant CYP51 as the query, we identified and validated the biosynthetic gene cluster (BGC) of 1. Additional genome mining of related BGCs with CYP51 led to production of the related lanomycin 2. The pathways for both 1 and 2 were identified from fungi not known to produce these compounds, highlighting the promise of the self-resistance enzyme (SRE) guided approach to bioactive natural product discovery.

Entities: Chemical

Mesh：

Substances：

Year: 2021 PMID： 33857369 PMCID： PMC8119659 DOI： 10.1021/jacs.1c01516

Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419

31 in total

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Journal: Appl Environ Microbiol Date: 2006-04 Impact factor: 4.792

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Journal: Chem Biol Date: 2014-02-20

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Journal: Chem Commun (Camb) Date: 2016-04-08 Impact factor: 6.222

4. Structural basis of human CYP51 inhibition by antifungal azoles.

Authors: Natallia Strushkevich; Sergey A Usanov; Hee-Won Park
Journal: J Mol Biol Date: 2010-02-10 Impact factor: 5.469

5. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans.

Authors: Volker Schroeckh; Kirstin Scherlach; Hans-Wilhelm Nützmann; Ekaterina Shelest; Wolfgang Schmidt-Heck; Julia Schuemann; Karin Martin; Christian Hertweck; Axel A Brakhage
Journal: Proc Natl Acad Sci U S A Date: 2009-08-06 Impact factor: 11.205

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Authors: A S Trenin
Journal: Bioorg Khim Date: 2013 Nov-Dec

7. Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway.

Authors: Nicholas Liu; Yiu-Sun Hung; Shu-Shan Gao; Leibniz Hang; Yi Zou; Yit-Heng Chooi; Yi Tang
Journal: Org Lett Date: 2017-06-13 Impact factor: 6.005

8. A Novel Y319H Substitution in CYP51C Associated with Azole Resistance in Aspergillus flavus.

Authors: R A Paul; S M Rudramurthy; J F Meis; J W Mouton; A Chakrabarti
Journal: Antimicrob Agents Chemother Date: 2015-07-27 Impact factor: 5.191

9. Fungal Highly Reducing Polyketide Synthases Biosynthesize Salicylaldehydes That Are Precursors to Epoxycyclohexenol Natural Products.

Authors: Ling Liu; Man-Cheng Tang; Yi Tang
Journal: J Am Chem Soc Date: 2019-12-05 Impact factor: 15.419