- McCulloch, K.M., McCranie, E.K., Smith, J.A., Sarwar ,M., Mathieu, J.L., Gitschlag, B.L., Du, Y., Bachmann, B.O., Iverson, T.M. Oxidative cyclizations in orthosomycin biosynthesis expand the known chemistry of an oxygenase superfamily. Proceedings of the National Academy of Sciences U S A. 2015 Aug 3 epub DOI.
The orthoester bond is an orthogonal means of linking saccharides in a highly active family of natural products call the orthosomycins. In collaboration with the Iverson group, we provide structural and biochemical evidence in support of a new class of enzymes, orthoester synthases, that we propose oxidize glycosidic linkages to orthoesters.
- Derewacz D.K., Covington B.C., McLean J.A., Bachmann B.O. Mapping Microbial Response Metabolomes for Induced Natural Product Discovery. ACS Chemical Biology. 2015, epub: DOI
This paper demonstrates how metabolomic inventories of bi-cultures are larger and more complex than their monoculture donors. A self organizing maps (SOM) algorithm was used to mine metabolomic data for features unique to co-culture and we reveal a new macrolactam polyketide, stimulated by mixed culture. We were grateful this work was reviewed in C&E News and Popular Science.
- Goodwin C.R., Covington B.C., Derewacz D.K., McNees C.R., Wikswo J.P., McLean JA, Bachmann B.O. Structuring Microbial Metabolic Responses to Multiplexed Stimuli via Self-Organizing Metabolomics Maps. Chemistry & Biology. 2015, 22, 567-568. DOI
A new way to specifically organize metabolites in microbial a “response-ome” by how they respond across a battery of conditions. Natural products betray themselves within metabolomes by how they respond via analysis of this multidimensional data set .
- DeGuire S.M., Earl D.C., Du Y., Crews B.A., Jacobs A.T., Ustione A., Daniel C., Chong K.M., Marnett L.J., Piston D.W., Bachmann B.O., Sulikowski G.A. Fluorescent Probes of the Apoptolidins and their Utility in Cellular Localization Studies. Angewandte Chemie. 2015 J 54(3), 961-4. DOI
In this work, genome editing of the Apoptolidin producing organism facilitated the generation of glycovariants for use in probe generation for this uniquely selective cytotoxic natural product.
- Stow, S.; Goodwin, C.; Kliman, M.; Bachmann, B.O.; McLean, J; Lybrand, T., 2014. A Distance Geometry Protocol to Generate Conformations of Natural Products to Structurally Interpret Ion Mobility-Mass Spectrometry Collision Cross Sections. The Journal of Physical Chemistry, 2014 118(48), 13812-20 DOI.
In this paper, a novel computation method was generated to model the gas phase conformations of natural product classes in the context of ion mobility mass spectrometry.
- Kramer, G.J., Mohd, A., Schwager, S.L., Masuyer, G., Acharya, K.R., Sturrock, E.D., and Bachmann, B.O. 2014. Interkingdom pharmacology of Angiotensin-I converting enzyme inhibitor phosphonates produced by actinomycetes. ACS medicinal chemistry letters 5, 346-351 DOI.
This study studies the “natural SAR” of the K-26 family of compounds via synthesizing all of the known natural K-26 family and assaying it against ACE. The SAR of ACE like enzymes against K-26 is also investigated revealing a paradoxical high selectivity for inhibition of eukaryotic ACE by the bacterial metabolite.
- Goodwin CR, Sherrod SD, Marasco CC, Bachmann BO, Schramm-Sapyta N, Wikswo JP, McLean JA. Phenotypic Mapping of Metabolic Profiles Using Self-Organizing Maps of High-Dimensional Mass Spectrometry Data. Analytical Chemistry. 2014 86, 6563-6571 DOI.
This paper provides a ground breaking method for using self organizing maps analytics to catalog metabolomic changes in mice exposed to cocaine.
- Birmingham, W.R., Starbird, C.A., Panosian, T.D. Nannemann, D.P., Iverson, T.M., Bachmann, B.O. Bioretrosynthetic construction of a didanosine biosynthetic pathway. Nature Chemical Biology. 2014 10, 392-399 DOI.
This work describes the first ever application of the retroevolution hypothesis to the generation of a biosynthetic pathway. This article was in the 98 percentile (ranked 1,296th) of the 88,792 tracked articles of a similar age in all journals, in the 93 percentile (ranked 3rd) of the 47 tracked articles of a similar age in Nature Chemical Biology in 2014.
- McCranie, E.K., Bachmann, B.O. Bioactive Oligosaccharide Natural Products. Natural Products Reports. 2014, Natural Product Reports. 2014, 31, 1026. DOI.
A review of the biosynthesis of oligosaccharide natural products, an under studied field of bioactive molecules.
- Derewacz, D.K., McNees, C.R., Scalmani, G., Covington, C.L., Shanmugam, G., Marnett, L.J., Polavarapu P.L., Bachmann, B.O. Structure and stereochemical determination of hypogeamicins from a cave-derived actinomycete. Journal of Natural Products. 2014, DOI.
The discovery of a new aromatic polyketide family from a cave actinomycete. The determination of stereochemistry used a quantum computational approach confirmed by chiroptical measurements.
- Bachmann B.O., Van Lanen S.G., Baltz R.H. Microbial genome mining for accelerated natural products discovery: is a renaissance in the making? Journal of Industrial Microbiology and Biotechnology. 2014 Feb;41(2):175-84 DOI.
An overview for a special issue on genome mining co-edited by Brian Bachmann, Steve VanLanen and Dick Balz.
- Al-Mestarihi A., Romo A., Liu H.W., Bachmann B.O. Nitrososynthase-triggered oxidative carbon-carbon bond cleavage in baumycin biosynthesis. Journal of the American Chemical Society. 2013. Aug 7;135(31):11457-60 DOI.
This work describes the discovery of a new class of biochemical reaction: a retro-oxime aldolase enzyme!
- Derewacz D.K., Goodwin C.R., McNees C.R., McLean J.A., Bachmann B.O. Antimicrobial drug resistance affects broad changes in metabolomic phenotype in addition to secondary metabolism. Proceeding of the National Academy of Sciences. 2013 Feb 5;110(6): 2336-41 DOI.
What happens to a microbes metabolome when it becomes resistant to antibiotics via acquisition of point mutations in the translation and transcriptional apparatus? Wholesale change and upregulation of antibiotic biosynthesis.
- Iverson T.M., Panosian T.D., Birmingham W.R, Nannemann D.P., Bachmann B.O. Molecular differences between a mutase and a phosphatase: investigations of the activation step in Bacillus cereus phosphopentomutase. Biochemistry. 2012 Mar 6; 51(9): 1964-75. DOI.
A dissection of the structural basis for the mechanism of phosphopentomutase, an enzyme we subsequently engineer to make nucleoside analogs
- Goodwin C.R., Fenn L.S., Derewacz D.K., Bachmann B.O., McLean J.A. Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products. J. Nat Prod. 2012 Jan 4. DOI.
The gas phase shape of natural products can betray their compound class. Here we show how peptides natural products have a smaller collision cross section, and how this parameter measure by ion mobility mass spectrometry can help accelerate discovery.
- Yu Du, Dagmara K. Derewacz, Sean M. Deguire, Jesse Teske, Jacques Ravel, Gary A. Sulikowski,* and Brian O. Bachmann* Biosynthesis of the Apoptolidins in Nocardiopsis sp. FU 40, Tetrahedron. 2011 In press DOI.
A description, analysis, and manipulation of the biosynthetic gene cluster of the highly potent and selectively cytotoxic macrolides known as the apoptolidins.
- Nannemann D.P., Birmingham W.R., Scism R.A., Bachmann B.O., Assessing directed evolution methods for the generation of biosynthetic enzymes with potential in drug biosynthesis.Future Med Chem. 2011 May;3(7):809-19.PMID: 21644826. PDF.
A quantitative analysis of the success directed evolution campaigns of biocatalytic enzymes reporting kinetic parameters over a 10 year period. Surprising results!
- Panosian, T.D., Nannemann, D.P., Watkins, G., Phelan, V.V., Mc Donald, W.H., Wadzinski, B.E., Bachmann, B.O., Iverson, T.M.. The Bacillus cereus phosphopentomutase is an alkaline phosphatase family member that exhibits an altered entry point into the catalytic cycle. J Biol Chem. J Biol Chem. 2011 Mar 11;286(10):8043-54. PMID: 21193409
- Vey, J.L.,Al-Mestarihi,A., Hu, Y.,Funk, M.A., Bachmann,B.O. and Iverson, T.M.. Mechanism of Amino Sugar Oxidation During Everninomycin Biosynthesis. Biochemistry. 2010 Nov 2;49(43):9306-17. PMID: 0866105
- Akif, M., Ntai, I., Sturrock, E.D., Isaac, R.E., Bachmann, B.O.,Ravi, A.., Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (An CE) from Drosophila melanogaster. Biochemical and Biophysical Research Communications 2010 PMID: 20599761
- Bachmann, B. O., Mc Nees, R., Melancon, B. J., Ghidu, V. P., Clark, R., Crews, B. C., Deguire, S. M., Marnett, L. J. and Sulikowski, G. A., Light-induced isomerization of apoptolidin A leads to inversion of C2-C3 double bond geometry. Organic Letters. 2010, 12, 2944-2947. PMID 20515014
- Panosian, T. D., Nannemann, D. P., Bachmann, B. O. and Iverson, T. M., Crystallization and preliminary X-ray analysis of a phosphopentomutase from Bacillus cereus. Acta Crystallographica F. 2010, 66, 811-814. PMID 20606280
- Du, Y., Gisselberg, J. E., Johnson, J. D., Lee, P. J., Prigge, S. T. and Bachmann, B. O., Lactococcus lactis fabH, encoding b-ketoacyl-acyl carrier protein synthase, can be functionally replaced by the Plasmodium falciparum congener. Applied and Environmental Microbiology. 2010, 76, 3959-3966. PMID 20418430
- Nannemann, D. P., Kaufmann, K. W., Meiler, J. and Bachmann, B. O., Design and directed evolution of a dideoxy purine nucleoside phosphorylase. Protein Engineering Design and Selection. 2010, 23, 607-616.PMID 20525731
- Reniere, M. L., Ukpabi, G. N., Harry, S. R., Stec, D. F., Krull, R., Wright, D. W., Bachmann, B. O., Murphy, M. E. and Skaar, E. P., The Isd G-family of haem oxygenases degrades haem to a novel chromophore. Molecular Microbiology. 2010, 75, 1529-1538. PMID 20180905
- Bachmann, B. O., Biosynthesis: is it time to go retro? (commentary). Nature Chemical Biology. 2010, 6, 390-393. PMID 20479744.
- Carter, M. D., Phelan, V. V., Sandlin, R. D., Bachmann, B. O. and Wright, D. W., Lipophilic mediated assays for b-hematin inhibitors. Combinatorial Chemistry & High Throughput Screening. 2010, 13, 285-292. PMID 20230372
- Scism, R. A. and Bachmann, B. O., Five-component cascade synthesis of nucleotide analogues in an engineered self-immobilized enzyme aggregate. Chembiochem. 2010, 11, 67-70. PMID 19918830
- Phelan, V. V., Du, Y., Mc Lean, J. A. and Bachmann, B. O., Adenylation enzyme characterization using g -18O4-ATP pyrophosphate exchange. Chemistry & Biology. 2009, 16, 473-478. PMID 19477411
- Bachmann, B. O. and Ravel, J., Chapter 8. Methods for in silico prediction of microbial polyketide and nonribosomal peptide biosynthetic pathways from DNA sequence data. Methods in enzymology. 2009, 458, 181-217. PMID 19374984
- Ghidu, V. P., Ntai, I., Wang, J., Jacobs, A. T., Marnett, L. J., Bachmann, B. O. and Sulikowski, G. A., Combined chemical and biosynthetic route to access a new apoptolidin congener. Organic Letters. 2009, 11, 3032-3034. PMID 19552384
- Ntai, I. and Bachmann, B. O., Identification of ACE pharmacophore in the phosphonopeptide metabolite K-26. Bioorganic & Medicinal Chemistry Letters. 2008, 18, 3068-3071. PMID 18096385
- Hu, Y., Phelan, V. V., Farnet, C. M., Zazopoulos, E. and Bachmann, B. O., Reassembly of anthramycin biosynthetic gene cluster by using recombinogenic cassettes. Chembiochem. 2008, 9, 1603-1608. PMID 18512205
- Hu, Y., Al-Mestarihi, A., Grimes, C. L., Kahne, D. and Bachmann, B. O., A unifying nitrososynthase involved in nitrosugar biosynthesis. Journal of the American Chemical Society. 2008, 130, 15756-15757.PMID 18983146
- Scism, R. A., Stec, D. F. and Bachmann, B. O., Synthesis of nucleotide analogues by a promiscuous phosphoribosyltransferase. Organic Letters. 2007, 9, 4179-4182. PMID 17854193
- Hu, Y., Phelan, V., Ntai, I., Farnet, C. M., Zazopoulos, E. and Bachmann, B. O., Benzodiazepine biosynthesis in Streptomyces refuineus. Chemistry and Biology. 2007, 14, 691-701. PMID 17584616
- Bachmann, B. O., Foundations for directed alkaloid biosynthesis (commentary). Chemistry and Biology. 2007, 14, 875-876. PMID 17719485
- Wilkinson, B. and Bachmann, B. O., Biocatalysis in pharmaceutical preparation and alteration. Current Opinion in Chemical Biology. 2006, 10, 169-176. ISI:000237000700013
- Sulikowski, M. M. and Bachmann, B. O., Designing a curriculum that goes beyond a list of topics (commentary). ACS Chemical Biology. 2006, 1, 489-491. PMID 17168533
- Ntai, I., Phelan, V. V. and Bachmann, B. O., Phosphonopeptide K-26 biosynthetic intermediates in Astrosporangium hypotensionis. Chemical Communications. 2006, 4518-4520. PMID 17283804
- Ntai, I., Manier, M. L., Hachey, D. L. and Bachmann, B. O., Biosynthetic origins of C-P bond containing tripeptide K-26. Organic Letters. 2005, 7, 2763-2765. ISI:000229952100062
- Bachmann, B. O., Decoding chemical structures from genomes (commentary). Nature Chemical Biology. 2005, 1, 244-245. PMID 16408048 (Commentary).