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Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl- S -carrier proteins in the pksX pathway of Bacillus subtilis

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Calderone, Christopher T., Kowtoniuk, Walter E., Kelleher, Neil L., Walsh, Christopher T., Dorrestein, Pieter C.·2006·Proceedings of the National Academy of Sciences

Abstract

The pksX gene cluster from Bacillus subtilis is predicted to encode the biosynthesis of an as yet uncharacterized hybrid nonribosomal peptide/polyketide secondary metabolite. We used a combination of biochemical and mass spectrometric techniques to assign functional roles to the proteins AcpK, PksC, PksL, PksF, PksG, PksH, and PksI, and we conclude that they act to incorporate an acetate-derived β-methyl branch on an acetoacetyl- S -carrier protein and ultimately generate a Δ 2 -isoprenyl- S -carrier protein. This work highlights the power of mass spectrometry to elucidate the functions of orphan biosynthetic enzymes, and it details a mechanism by which single-carbon β-branches can be inserted into polyketide-like structures. This pathway represents a noncanonical route to the construction of prenyl units and serves as a prototype for the intersection of isoprenoid and polyketide biosynthetic manifolds in other natural product biosynthetic pathways.

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Metadata

Authors
Calderone, C. T., Kowtoniuk, W. E., Kelleher, N. L., Walsh, C. T., & Dorrestein, P. C.
Venue
Proceedings of the National Academy of Sciences
Published
2006-06-13
Volume
103
Issue
24
Pages
8977-8982
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2099302541
Cited by
176
References
2
FWCI
10.57
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl- S -carrier proteins in the pksX pathway of Bacillus subtilis. https://app.cochat.ai/papers/10.1073/pnas.0603148103
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Calderone, C. T., Kowtoniuk, W. E., Kelleher, N. L., Walsh, C. T., & Dorrestein, P. C. (2006). Convergence of isoprene and polyketide biosynthetic machinery: Isoprenyl- S -carrier proteins in the pksX pathway of Bacillus subtilis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0603148103

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