Concise Biosynthesis of Antifungal Papulacandins
We report the complete biosynthesis of antifungal papulacandins through heterologous expression and enzymatic assays. The papulacandin biosynthesis follows a convergent five-component strategy, involving a linear polyketide chain that is synthesized and installed to the aryl-glucoside by a polyketide synthase fused with a C-terminal acyltransferase domain. The formation of the challenging tricyclic benzannulated spiroketal core is initiated by the <i>C</i>-glycosylation of 5-(hydroxymethyl)resorcinol, followed by spirocyclization catalyzed by a Fe(II)/α-ketoglutarate-dependent oxygenase PpcE.
Authors
- Niandi Zhang
- Zhiqiang An (ORCID: https://orcid.org/0000-0001-9309-2335)
- Zhuan Zhang (ORCID: https://orcid.org/0000-0002-3300-3035)
- Gerald F. Bills (ORCID: https://orcid.org/0000-0003-2352-8417)
- Mingxin Zheng (ORCID: https://orcid.org/0000-0001-8461-8980)
- Lingyan Wang (ORCID: https://orcid.org/0000-0001-9236-7229)
- Jinmei Li (ORCID: https://orcid.org/0000-0003-3367-6659)
- Meihui Zhao
- Chao Yu (ORCID: https://orcid.org/0000-0002-6929-6693)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- Brown Foundation (US)
- Pharmaceutical Biotechnology (Czechia) (CZ)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1021/jacs.4c13101
- Citations
- 3
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 4.18
Funders
- Welch Foundation
- National Institutes of Health
- Fundamental Research Funds for the Central Universities