Examination of Potential Exceptions to the F and S Biosynthetic Classification of Fused‐Ring Aromatic Polyketides

Abstract

The reported acetate-derived labelling of the fungal naphthalene γ-pyrone fonsecin, two streptomycete dodecaketide αpyrones TW93f and TW93g, and the streptomycete phenanthraquinones piloquinone, murayaquinone and haloquinone appear to be exceptions to the generalisation that fungi and streptomycetes produce fused-ring aromatic polyketides by different modes of cyclisation. A review of their 1) originally assigned formulae, 2) [ C ]acetate-derived labelling patterns, and 3) modes of cyclisation leads to the recognition of feasible alternative chemical structures or biosynthetic pathways, which are in accord with the originally proposed classification system.

An interpreted atlas of biosynthetic gene clusters from 1,000 fungal genomes

“…We quantified the dramatic differences in bacterial versus fungal NRPS and PKS assembly line logic. Bacterial and fungal PKS enzymes are known to differ in aromatic polyketide assembly logic (47,48), and the vast majority of characterized fungal PKS enzymes are iterative (49). This iterative PKS pattern observed in characterized fungal PKS enzymes holds true across this dataset, with fungal PKSs most often encoding a single-backbone PKS enzyme, compared to bacterial PKS BGCs which contain a median of 1.7 PKS backbone enzymes per cluster (Fig.…”

Marine Bacterial Aromatic Polyketides From Host-Dependent Heterologous Expression and Fungal Mode of Cyclization

“…It is intriguing to discover the anthraquinone derivative 3 in a bacterium. It was speculated that fundamentally different cyclization strategies were employed by bacterial and fungal type II PKSs to biosynthesize structurally similar APKs with fused-rings (Thomas, 2001 , 2016 ). The first-ring cyclization modes were classified into F-mode for fungi to contain two intact acetate units, and S-mode for bacteria to contain three intact acetate units in the first cyclized phenol ring (Supplementary Figure 7 ) (Thomas, 2001 , 2016 ; Zhou et al, 2010 ).…”

“…It was speculated that fundamentally different cyclization strategies were employed by bacterial and fungal type II PKSs to biosynthesize structurally similar APKs with fused-rings (Thomas, 2001 , 2016 ). The first-ring cyclization modes were classified into F-mode for fungi to contain two intact acetate units, and S-mode for bacteria to contain three intact acetate units in the first cyclized phenol ring (Supplementary Figure 7 ) (Thomas, 2001 , 2016 ; Zhou et al, 2010 ). This fundamental difference was reinforced by the discovery of three divergent first-ring cyclization strategies to converge in generating the same metabolite chrysophanol, namely F-mode (C6/C11) in fungi and plants (Bringmann et al, 2006 ), and S-mode (C5/C10) or S′-mode (C7/C12) in bacteria (Bringmann et al, 2006 , 2009 ).…”

“…Several bacterial fused-ring APKs were found as exceptions to be putatively derived from fungal F-mode cyclizations, such as TW93f and Tw93g (Shen et al, 1999 ), piloquinone (Polonsky and Lederer, 1963 ), murayaquinone (Gould et al, 1997 ), and haloquinone (Krone et al, 1981 ). However, it was recently discussed that evidence should be provided for these exceptions to either validate the structures (TW93f and Tw93g), or confirm the folding pattern by detailed labeling studies (Thomas, 2016 ). In contrast, the presence of the six-membered lactone ring in fluoquinone ( 3 ) strongly suggested that 3 should be derived from the first-ring cyclization via C6/C11 ( cyclization pattern III : C6/C11, C4/C13, C2/C15, C17-OH/C1, Figure 3C ).…”

“…The fungal natural product dermolactone, highly similar to 3 , was confirmed to be derived from the F-mode of first ring cyclization (Figure 3D ) (Gill and Gimenez, 1990 ). Thus, fluoquinone ( 3 ) represents an exception as a bacterial F-mode (fungal mode) to the F and S biosynthetic classifications of fused ring APKs (Thomas, 2001 , 2016 ).…”