Posters

EvoSelect poster 2025Presented at ACS "Driving Sustainability in Pharma and Allied Industries" workshop, ML for Biocatalysis Workshop 2025, and IBPRO (Mar 25).

 

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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