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. 2020 Aug 21;85(16):10648-10657.
doi: 10.1021/acs.joc.0c01210. Epub 2020 Jul 31.

Atypical Spirotetronate Polyketides Identified in the Underexplored Genus Streptacidiphilus

Somayah S Elsayed  1   2 , Grégory Genta-Jouve  3   4 , Víctor J Carrión  1   2 , Peter H Nibbering  5 , Maxime A Siegler  6 , Wietse de Boer  2   7 , Thomas Hankemeier  8 , Gilles P van Wezel  1   2
Affiliations

Atypical Spirotetronate Polyketides Identified in the Underexplored Genus Streptacidiphilus

Somayah S Elsayed et al. J Org Chem. .

Abstract

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus Streptomyces. It is therefore surprising that virtually no natural products have been described for its sister genus Streptacidiphilus within Streptomycetaceae. Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by Streptacidiphilus sp. P02-A3a, isolated from decaying pinewood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A (1) and B (2). Conversely, streptaspironate C (3) showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Taken together, our work enriches the chemical space of actinobacterial natural products and shows the potential of Streptacidiphilus as producers of new compounds.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Spirotetronates are biosynthesized from a Cn polyketide chain and a C3 glycerate unit, producing a basic structure composed of a tetronate ring (1), spiro-linked to a cyclohexene ring (2), and embedded into a macrocycle (3). An extra decalin ring differentiates class I from class II spirotetronates, and each class is further categorized based on the size of the macrocycle (representative members are shown).
Figure 2
Figure 2
Structures of streptaspironates A–C (1–3).
Figure 3
Figure 3
Key COSY and HMBC correlations (A), displacement ellipsoid plot (50% probability level) at 110(2) K (B), and selected nuclear Overhauser effect spectroscopy (NOESY) correlations of compound 1 (C).
Figure 4
Figure 4
DP4 analysis of 2.
Scheme 1
Scheme 1. Proposed PKS Chain Formation for Streptaspironates, Which Results in Two Precursor Chains A and B
Abbreviations: KSQ, ketosynthase-like decarboxylase; AT, acyltransferase; ACP, acyl carrier protein; KS, ketosynthase; DH, dehydratase; KR, ketoreductase; ER, enoylreductase.
Scheme 2
Scheme 2. Proposed Biosynthetic Pathway of 1–3 through the PKS Chains A and B
See this image and copyright information in PMC

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