cis-Delta(2,3)-double bond of phoslactomycins is generated by a post-PKS tailoring enzyme.

Journal of the American Chemical Society
Nadaraj PalaniappanKevin Reynolds

Abstract

The antifungal phoslactomycins (PLM A-F), produced by Streptomyces sp. HK803, are structurally unusual in that three of their four double bonds are in the cis form (Delta12,13, Delta14,15, Delta2,3). The PLM polyketide synthase (PKS) has the predicted dehydratase catalytic domain in modules 1, 2, and 5 required for establishing two of these cis double bonds (Delta12,13, Delta14,15), as well as the only trans Delta6,7 double bond. By contrast, the formation of the cis Delta2,3 in the unsaturated lactone moiety of PLMs has presented an enigma because the predicted dehydratase domain in module 7 is absent. Herein, we have demonstrated that the plmT2 gene product, with no homology to PKS dehydratase domains, is required for efficient formation of the cis Delta2,3 alkene. A series of new PLM products in which the C3 hydroxyl group is retained are made in plmT2 deletion mutants. In all of these cases, however, the hydroxyl group is esterified with malonic acid. These malonylated PLM products are converted to the corresponding cis Delta2,3 PLM products and acetic acid by a facile base-catalyzed decarboxylative elimination reaction. Complete or partial restoration of natural PLM production in a plmT2 deletion mutant can be accomplished...Continue Reading

References

Sep 8, 2001·Natural Product Reports·J Staunton, K J Weissman
Jul 10, 2003·Chembiochem : a European Journal of Chemical Biology·Patrick Caffrey
Dec 6, 2005·The Journal of Antibiotics·Suparna Das ChoudhuriKevin A Reynolds
Jan 6, 2006·The Journal of Antibiotics·Zhihao HuHugo Gramajo
Apr 13, 2006·Journal of Industrial Microbiology & Biotechnology·Mohini GhatgeKevin Reynolds

❮ Previous
Next ❯

Citations

Dec 5, 2012·Chemical Reviews·Jason W Labonte, Craig A Townsend
Jul 29, 2009·Natural Product Reports·Alexander Koglin, Christopher T Walsh
Nov 10, 2015·Applied Microbiology and Biotechnology·Haotong Chen, Liangcheng Du
Dec 17, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aida DroceJens Laurids Sørensen
Jul 22, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·David H Kwan, Frank Schulz
Jun 11, 2009·Angewandte Chemie·Christian Hertweck
Mar 23, 2017·Beilstein Journal of Organic Chemistry·Kira J Weissman
Aug 26, 2016·Beilstein Journal of Organic Chemistry·Franziska Hemmerling, Frank Hahn
Mar 21, 2009·Chembiochem : a European Journal of Chemical Biology·Chaoxuan LiWendy L Kelly
Nov 15, 2011·Chembiochem : a European Journal of Chemical Biology·Marie E YurkovichPeter F Leadlay
Apr 8, 2011·Chembiochem : a European Journal of Chemical Biology·Olivia VergnolleJennifer N Andexer
Jan 22, 2021·Natural Product Reports·Zhiyong Yin, Jeroen S Dickschat
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Songya ZhangTao Liu
Mar 13, 2014·Journal of the American Chemical Society·Hai-Yan HeGong-Li Tang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.