PPIase inhibitors

mTOR and FKBP inhibitors (Rapamycin analogues)

'Rational design of improved anti-proliferative rapalogs accessible through biosynthetic medicinal chemistry'. Gregory et al., Chem. Sci., 2013, 4, 1046-1052 (http://pubs.rsc.org/en/Content/ArticleLanding/2013/SC/C2SC21833J).

'Recombinant strains for the enhanced production of bioengineered rapalogs', Kendrew et al, . Metab. Eng., 2013, 15, 167-173 (http://www.ncbi.nlm.nih.gov/pubmed/23164580).

'Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate', Andexer et al., Proc. Natl. Acad. Sci. USA., 2011, 108, 4776-81 (http://www.ncbi.nlm.nih.gov/pubmed/21383123).

'An expeditious route to fluorinated rapamycin analogues by utilising mutasynthesis', Goss et al., ChemBioChem, 2010, 11(5), 698-702, (http://www.ncbi.nlm.nih.gov/pubmed/20186904).

'Roles of rapH and rapG in positive regulation of rapamycin biosynthesis in Streptomyces hygroscopicus' Kuscer et al., J. Bacteriol., 2007, 189, 4756-4763 (http://www.ncbi.nlm.nih.gov/pubmed/17468238).

'Rapamycin biosynthesis: elucidation of gene product function', Gregory et al., Org. Biomol. Chem., 2006, 4, 3565–3568 (http://www.ncbi.nlm.nih.gov/pubmed/16990929).

'Mutasynthesis of rapamycin analogues through the manipulation of a gene governing starter unit biosynthesis', Gregory et al., Angew. Chem. Int. Ed. Engl., 2005, 44, 4757-4760 (http://www.ncbi.nlm.nih.gov/pubmed/15977283).

'Site specific bioalkylation of rapamycin by the rapM 16-O-methyltransferase', Law et al., Chem. Sci, 2015, 6, 2885-2892 (http://pubs.rsc.org/en/content/articlehtml/2015/sc/c5sc00164a).

Calcineurin and FKBP inhibitors (FK506 and FK520 analogues)

'Novel FK506 and FK520 analogues via mutasynthesis: mutasynthon scope and product characteristics', Moss et al., Med. Chem. Comm., 2013, 4, 324-331 (http://pubs.rsc.org/en/content/articlelanding/2013/md/c2md20266b).

Cyclophilin inhibitors (Sanglifehrin analogues)

'Bioengineering and semisynthesis of an optimised cyclophilin inhibitor for treatment of chronic viral infection', Hansson et al., Chemistry and Biology, 2015, 22, 1-8

'Multiple mutations in hepatitis C virus NS5A domain II are required to confer a significant level of resistance to Alisporivir', Garcia-Rivera et al., Antimicrob. Agents Chemother., 2012, 56, 5113-5121 (http://www.ncbi.nlm.nih.gov/pubmed/22802259).

'Sangamides, a new class of cyclophilin-inhibiting host-targeted antivirals for treatment of HCV infection', Moss et al., Med. Chem. Comm., 2012, 3, 938-943 (http://pubs.rsc.org/en/Content/ArticleLanding/2012/MD/c1md00227a).

 'Preclinical characterization of naturally occurring polyketide cyclophilin inhibitors from the sanglifehrin family', Gregory et al., Antimicrob. Agents Chemother., 2011, 55, 1975-1981 (http://www.ncbi.nlm.nih.gov/pubmed/21383094).

Technology exemplification

Spliceosome inhibitors (Borellidin analogues)

'Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor', Mirando et al., Sci. Rep., 2015, 5, 13160 (http://www.ncbi.nlm.nih.gov/pubmed/26271225).

'Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo', Novoa et al., Proc. Natl. Acad. Sci. USA, 2014, 111(51), E5508-17, (http://www.ncbi.nlm.nih.gov/pubmed/25489076).

'Borrelidin modulates the alternative splicing of VEGF in favour of anti-angiogenic isoforms', Woolard et al., Chem. Sci., 2011, 2, 273-278 (http://www.ncbi.nlm.nih.gov/pubmed/22822423).

'Separation of anti-angiogenic and cytotoxic activities of borrelidin by modification at the C-17 side chain', Wilkinson et al., Bioorg. Med. Chem. Lett., 2006, 16, 5814-5817 (http://www.ncbi.nlm.nih.gov/pubmed/16962775).

Hsp90 inhibitors (Macbecin analogues)

'Optimizing natural products by biosynthetic engineering: discover of non-quinone Hsp90 inhibitors', Zhang et al., J. Med. Chem., 2008, 51, 5494-5497 (http://www.ncbi.nlm.nih.gov/pubmed/18800759).

'Molecular characterisation of macbecin as an Hsp90 inhibitor', Martin et al., J. Med. Chem., 2008, 51, 2853-2857 (http://www.ncbi.nlm.nih.gov/pubmed/18357975).

Bacterial ribosome inhibitors (Erythromycin analogues)

'Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties', Schell et al., Org. Biomol. Chem., 2008, 6, 3315-27 (http://www.ncbi.nlm.nih.gov/pubmed/18802638).

Insect nicotinic acetylcholine receptors (Spinosyn analogues)

'Glycosylation engineering of spinosyn analogues containing an L-olivose moiety', Gaisser et al., Org. Biomol. Chem., 2009, 7, 1705-1708 (http://www.ncbi.nlm.nih.gov/pubmed/19343260).

Other example publications

'Biosynthesis of the novel macrolide antibiotic anthracimycin', Alt et al., ACS Chem. Biol., 2015, 10(11), 2468-79 (http://www.ncbi.nlm.nih.gov/pubmed/26349074).

'Minimum information about a biosynthetic gene cluster', Medema et al., Nat. Chem. Biol., 2015, 11(9), 625-31, (http://www.ncbi.nlm.nih.gov/pubmed/26284661).

'Bioengineering natural product biosynthetic pathways for therapeutic applications', Wu et al., 2012, 23(6), 931-40, (http://www.ncbi.nlm.nih.gov/pubmed/22487048).

'Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency', Ehinger et al., Nat. Comm., 2016, 7, 12317, (https://www.nature.com/articles/ncomms12317)

'Diversity oriented biosynthesis via accelerated evolution of modular gene clusters' Wlodek et al., Nat. Comm., 2017, 8, 1206, (https://www.nature.com/articles/s41467-017-01344-3)


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