DOI: 10.1073/pnas.0805530105. 2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by <i>Streptomyces coelicolor</i> genome mining

2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining

10.1073/pnas.0805530105

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

All of the genetic elements necessary for the production of the antibiotic methylenomycin (Mm) and its regulation are contained within the 22-kb mmy-mmf gene cluster, which is located on the 356-kb linear plasmid SCP1 of Streptomyces coelicolor A3( 2 ). A putative operon of 3 genes within this gene cluster, mmfLHP , was proposed to direct the biosynthesis of an A-factor-like signaling molecule, which could play a role in the regulation of Mm biosynthesis. The mmfLHP operon was expressed under the control of its native promoter in S. coelicolor M512, a host lacking the SCP1 plasmid, and the ability to produce prodiginine and actinorhodin antibiotics. Comparative metabolic profiling led to the identification and structure elucidation of a family of 5 new 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (AHFCAs), collectively termed Mm furans (MMFs), as the products of the mmfLHP genes. MMFs specifically induce the production of the Mm antibiotics in S. coelicolor . Comparative genomics analyses and searches of the natural product chemistry literature indicated that other streptomycetes may produce AHFCAs, suggesting that they could form a general class of antibiotic biosynthesis inducers in Streptomyces species, with analogous functions to the better known γ-butyrolactone regulatory molecules.

Bibliography

Corre, C., Song, L., OâRourke, S., Chater, K. F., & Challis, G. L. (2008). 2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining. Proceedings of the National Academy of Sciences, 105(45), 17510â17515.

Authors 5

Christophe Corre (first)
Lijiang Song (additional)
Sean O'Rourke (additional)
Keith F. Chater (additional)
Gregory L. Challis (additional)

References 29 Referenced 135

10.1016/j.mib.2005.02.016
AL Demain, Induction of microbial secondary metabolism. Int Microbiol 1, 259–264 (1998). / Int Microbiol / Induction of microbial secondary metabolism by Demain AL (1998)
10.1016/j.mib.2006.04.003
10.1111/j.1462-2920.2007.01314.x
10.2183/pjab.83.277
10.1073/pnas.0607472104
10.1038/417141a
10.1111/j.1574-6968.1997.tb12756.x
LN Anisova, et al., Regulators of the development in Streptomyces coelicolor A3(2). Izv Akad Nauk SSSR Ser Biol 1, 98–108 (1984). / Izv Akad Nauk SSSR Ser Biol / Regulators of the development in Streptomyces coelicolor A3(2) by Anisova LN (1984)
OV Efremenkova, LN Anisova, YE Bartoshevich, Regulators of differentiation in actinomycetes. Antibiot Med Biotekhnol 9, 687–707 (1985). / Antibiot Med Biotekhnol / Regulators of differentiation in actinomycetes by Efremenkova OV (1985)
10.1074/jbc.275.15.11010
10.1046/j.1365-2958.2001.02562.x
10.1111/j.1365-2958.2005.04543.x
10.1007/s00203-006-0176-7
10.1099/mic.0.2006/004432-0
10.1111/j.1365-2958.2003.03949.x
10.1002/cbic.200500243
10.1046/j.1365-2958.1999.01579.x
10.1016/j.chembiol.2007.01.001
10.1021/jm700948z
10.1073/pnas.0337542100
10.1038/nchembio731
10.1021/ja065247w
10.1074/jbc.M710421200
10.7164/antibiotics.53.944
10.1002/(SICI)1099-0690(200003)2000:6<929::AID-EJOC929>3.0.CO;2-U
10.1128/JB.187.11.3795-3799.2005
10.1038/nbt820
10.1093/nar/gng071

Dates

Type	When
Created	16 years, 9 months ago (Nov. 6, 2008, 9:25 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:15 p.m.)
Indexed	6 days, 5 hours ago (Aug. 21, 2025, 12:50 p.m.)
Issued	16 years, 9 months ago (Nov. 11, 2008)
Published	16 years, 9 months ago (Nov. 11, 2008)
Published Online	16 years, 9 months ago (Nov. 11, 2008)
Published Print	16 years, 9 months ago (Nov. 11, 2008)

Funders 0

None

BibTeX

@article{Corre_2008, title={2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining}, volume={105}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0805530105}, DOI={10.1073/pnas.0805530105}, number={45}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Corre, Christophe and Song, Lijiang and O’Rourke, Sean and Chater, Keith F. and Challis, Gregory L.}, year={2008}, month=nov, pages={17510–17515} }

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  "abstract": "<jats:p>\n            All of the genetic elements necessary for the production of the antibiotic methylenomycin (Mm) and its regulation are contained within the 22-kb\n            <jats:italic>mmy-mmf</jats:italic>\n            gene cluster, which is located on the 356-kb linear plasmid SCP1 of\n            <jats:italic>Streptomyces coelicolor</jats:italic>\n            A3(\n            <jats:xref ref-type=\"bibr\">2</jats:xref>\n            ). A putative operon of 3 genes within this gene cluster,\n            <jats:italic>mmfLHP</jats:italic>\n            , was proposed to direct the biosynthesis of an A-factor-like signaling molecule, which could play a role in the regulation of Mm biosynthesis. The\n            <jats:italic>mmfLHP</jats:italic>\n            operon was expressed under the control of its native promoter in\n            <jats:italic>S. coelicolor</jats:italic>\n            M512, a host lacking the SCP1 plasmid, and the ability to produce prodiginine and actinorhodin antibiotics. Comparative metabolic profiling led to the identification and structure elucidation of a family of 5 new 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (AHFCAs), collectively termed Mm furans (MMFs), as the products of the\n            <jats:italic>mmfLHP</jats:italic>\n            genes. MMFs specifically induce the production of the Mm antibiotics in\n            <jats:italic>S. coelicolor</jats:italic>\n            . Comparative genomics analyses and searches of the natural product chemistry literature indicated that other streptomycetes may produce AHFCAs, suggesting that they could form a general class of antibiotic biosynthesis inducers in\n            <jats:italic>Streptomyces</jats:italic>\n            species, with analogous functions to the better known \u03b3-butyrolactone regulatory molecules.\n          </jats:p>",
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