Details:

Alternative Title:
J Am Chem Soc
Publisher's site:
http://dx.doi.org/10.1021/jacs.6b01528
Personal Author:
Gao, Shu-Shan ; Duan, Abing ; Xu, Wei ; Yu, Peiyuan ; Hang, Leibniz ; ... More +
Gao, Shu-Shan ; Duan, Abing ; Xu, Wei ; Yu, Peiyuan ; Hang, Leibniz ; Houk, K. N. ; Tang, Yi Less -
Description:
Phenalenones are polyketide natural products that display diverse structures and biological activities. The core of phenalenones is a peri-fused tricyclic ring system cyclized from a linear polyketide precursor via an unresolved mechanism. Toward understanding the unusual cyclization steps, the phn biosynthetic gene cluster responsible for herqueinone biosynthesis was identified from the genome of Penicillium herquei. A nonreducing polyketide synthase (NR-PKS) PhnA was shown to synthesize the heptaketide backbone and cyclize it into the angular, hemiketal-containing naphtho-γ-pyrone prephenalenone. The product template (PT) domain of PhnA catalyzes only the C4-C9 aldol condensation, which is unprecedented among known PT domains. The transformation of prephenalenone to phenalenone requires an FAD-dependent monooxygenase (FMO) PhnB, which catalyzes the C2 aromatic hydroxylation of prephenalenone and ring opening of the γ-pyrone ring simultaneously. Density functional theory calculations provide insights into why the hydroxylated intermediate undergoes an aldol-like phenoxide-ketone cyclization to yield the phenalenone core. This study therefore unveiled new routes and biocatalysts for polyketide cyclization.
Subject:
[+]
Article
Catalysis
Chromatography, Liquid
Cyclization
Flavins
Fungi
Molecular Structure
Multigene Family
Oxygenases
Phenalenes
Polyketide Synthases

Source:
J Am Chem Soc. 138(12):4249-4259.
Pubmed ID:
26978228
Pubmed Central ID:
PMC4988900
Document Type:
Journal Article
Funding:
DP1 GM106413/GM/NIGMS NIH HHS/United States ; R01 GM085128/GM/NIGMS NIH HHS/United States ; 1DP1GM106413/DP/NCCDPHP CDC HHS/United States ; 1R01GM085128/GM/NIGMS NIH HHS/United States
DP1 GM106413/GM/NIGMS NIH HHS/United States ; R01 GM085128/GM/NIGMS NIH HHS/United States ; 1DP1GM106413/DP/NCCDPHP CDC HHS/United States ; 1R01GM085128/GM/NIGMS NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:b64b0a502d3b580f118a4df043be848f83f0a8ce76accb962b3e293b8c5b735d
File Type:

Supporting Files

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