Publications
2019
Yasi E., Allen A., Sugianto W., Peralta-Yahya P. Identification of three antimicrobials activating serotonin receptor 4 in colon cells ACS Synth Biol , Article ASAP, DOI: 10.1021/acssynbio.9b00310, 2019
In the news: GaTech
Yasi E., Allen A., Sugianto W., Peralta-Yahya P. Identification of three antimicrobials activating serotonin receptor 4 in colon cells ACS Synth Biol , Article ASAP, DOI: 10.1021/acssynbio.9b00310, 2019
In the news: GaTech
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The serotonin receptor 4 (5-HTR4) is expressed throughout the gastrointestinal tract and its agonists are used in the treatment of irritable bowel syndrome with constipation (IBS-C). Today, there are no rapid assays for the identification of 5-HTR4 agonists. Here, we developed a 5-HTR4 assay capable of testing one compound per second and used it to screen >1,000 chemicals and identified three ligands (hordenine, halofuginone and revaprazan) that result in increased colon cell motility or wound healing. This assay can be used to screen larger pharmaceutical libraries to identify novel treatments for IBS-C. This work shows that antimicrobials interact not only with the gut microbiota, but also with the human host.
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Yasi E., Eisen A., Wang H., Sugianto W., Minniefield A., Hoover K., Branham P., Peralta-Yahya P. Rapid deorphanization of human olfactory receptors in yeast, Biochemistry, 58, 2160-2166, 2019
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Olfactory receptors (ORs) are expressed beyond the olfactory tissue. A key challenge in studying their role is the fact that the majority of ORs are orphaned (i.e. they have no known ligands). Here, we used our GPCR-based yeast sensor strain to generate sensors for 7 ORs highly expressed in the colon. We screened the 7 colon ORs against a 57-member chemical panel and successfully deorphanized 2 of them: OR2T4 and OR10S1. Our breakthrough will allow the elucidation of the role of these receptors in the colon.
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2018
Sarria S., Bartholow T., Verga A., Burkart M., Peralta-Yahya P. Matching protein interfaces for improved medium-chain fatty acid production, ACS Synth Biol, 7, 1179-1187, 2018.
Sarria S., Bartholow T., Verga A., Burkart M., Peralta-Yahya P. Matching protein interfaces for improved medium-chain fatty acid production, ACS Synth Biol, 7, 1179-1187, 2018.
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Microbial production of chemicals relies on the introduction of heterologous enzymes (e.g. from plants) into host organisms (e.g. Escherichia coli). Often, little attention is paid to the interaction between the heterologous and host enzymes. Here, we optimized the interphase of the E. coli's acyl carrier protein (ACP) and Acineyobacter baylyi thioesterase to improve medium-chain fatty acid titers more than 3-fold. Simply engineering the interface between heterologous and host enzymes is a viable strategy to increase chemical titers.
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2017
Sarria S., Kruyer N., Peralta-Yahya P. Microbial synthesis of medium-chain chemicals form renewables, Nat Biotechnol, 35, 1158-1166, 2017.
Ehrenworth A.M., Claiborne T., Peralta-Yahya P. Medium-throughput screen of microbially produced serotonin via a GPCR-based sensor, Biochemistry, 56, 5471-5475, 2017.
Sarria S., Kruyer N., Peralta-Yahya P. Microbial synthesis of medium-chain chemicals form renewables, Nat Biotechnol, 35, 1158-1166, 2017.
Ehrenworth A.M., Claiborne T., Peralta-Yahya P. Medium-throughput screen of microbially produced serotonin via a GPCR-based sensor, Biochemistry, 56, 5471-5475, 2017.
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A key limitation in the microbial production of chemicals is the throughput at which strains can be screened for chemical production. Chemical biosensors that convert chemical detection to a fluorescent output can enable high-throughput metabolic engineering applications. Here, we engineered a yeast-based serotonin sensor, used it to detect microbially produced serotonin, and validated it for medium-throughput screening applications.
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Ehrenworth A., Haines M., Wong A., Peralta-Yahya P. Quantifying the efficiency of Saccharomyces cerevisiae translocation tags,
Biotechnol Bioeng, 114, 2628-2636, 2017.
Kruyer N., Peralta-Yahya P. Metabolic engineering strategies to bio-adipic acid production, Curr Opin Biotechnol, 45, 136-143, 2017.
Ehrenworth A., Peralta-Yahya P. Accelerating the semi-synthesis of alkaloid-based drugs through metabolic engineering. Nat Chem Biol, 13, 249-258, 2017. In the news: GaTech COS, Phys.org, Health medicinet
Biotechnol Bioeng, 114, 2628-2636, 2017.
Kruyer N., Peralta-Yahya P. Metabolic engineering strategies to bio-adipic acid production, Curr Opin Biotechnol, 45, 136-143, 2017.
Ehrenworth A., Peralta-Yahya P. Accelerating the semi-synthesis of alkaloid-based drugs through metabolic engineering. Nat Chem Biol, 13, 249-258, 2017. In the news: GaTech COS, Phys.org, Health medicinet
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A number of pharmaceuticals are obtained via chemical derivatization of plant natural products. Today, plant pathways can be reconstituted in microbes and using engineered enzymes. Modified natural products can be produced to more rapidly and cost-effectively access pharmaceuticals. Here, we analyzed more than 2,000 FDA approved drugs and proposed pathways and engineered enzymes to produce modified plant alkaloids to accelerate the semi synthesis of 7 pharmaceuticals on the market.
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2015
Ehrenworth A., Sarria S., Peralta-Yahya P. Pterin-dependent mono-oxidation for the microbial synthesis of a modified monoterpene indole alkaloid ACS Synth Biol, 4, 1295-1307, 2015. In the news: Petit Institute News
Ehrenworth A., Sarria S., Peralta-Yahya P. Pterin-dependent mono-oxidation for the microbial synthesis of a modified monoterpene indole alkaloid ACS Synth Biol, 4, 1295-1307, 2015. In the news: Petit Institute News
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Anticancer and antimalarial agents are found among plant alkaloids. Isolation of alkaloids from plants is challenging due to their low accumulation and difficult separation from other similar compounds. To become pharmaceuticals, alkaloids often need to be derivatized to increase bioavailability and reduce toxicity. Here, we engineered the first microbial platform for the production of a modified monoterpene indole alkaloid from simple sugars.
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Ort DR, Merchant SS, Alric, Blankenship RE, Bock R, Croce R, Hanson MR, Hibberd JM, Long SP, Moore TA, Moroney J, Niyogi KK, Parry MA,
Peralta-Yahya P., Prince RC, Redding KE, Spalding MH, van Wijk KJ, Vermaas WF, von Caemmerer S, Weber AP, Yeates TO, Yuan JS, Zhu XG.
Redesigning photosynthesis to sustainably meet global food and bioenergy demand, Proc. Natl Acad Sci USA, 112, 8529-36, 2015.
In the news: Gizmodo
Mukherjee K., Bhattacharyya S., Peralta-Yahya, P. GPCR-based chemical sensors for medium-chain fatty acids, ACS Synth Biol, 4, 1261-9, 2015.
In the news: Petit Institute News
Peralta-Yahya P., Prince RC, Redding KE, Spalding MH, van Wijk KJ, Vermaas WF, von Caemmerer S, Weber AP, Yeates TO, Yuan JS, Zhu XG.
Redesigning photosynthesis to sustainably meet global food and bioenergy demand, Proc. Natl Acad Sci USA, 112, 8529-36, 2015.
In the news: Gizmodo
Mukherjee K., Bhattacharyya S., Peralta-Yahya, P. GPCR-based chemical sensors for medium-chain fatty acids, ACS Synth Biol, 4, 1261-9, 2015.
In the news: Petit Institute News
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Chemical biosensors convert chemical detection to a fluorescent or colorimetric output, enabling the screening of microbially produced chemicals up to 5 orders of magnitude faster than mass spectrometry methods. Here, we developed a platform for the generation of G-protein coupled receptor (GPCR)-based sensors in yeast.
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Peralta-Yahya P. Biosensor keep DOPA on track, News & Views, Nat Chem Biol, 11, 450-1, 2015. In the news: PBS NewsHour, Science Magazine, Science News
2014
Sarria S., Wong B., Garía Martín H., Keasling J., Peralta-Yahya P. Microbial synthesis of pinene, ACS Synth Biol, 3, 466-75, 2014.
In the news: Science Daily, Popular Science, Scientific American, Chemical and Engineering News
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2014
Sarria S., Wong B., Garía Martín H., Keasling J., Peralta-Yahya P. Microbial synthesis of pinene, ACS Synth Biol, 3, 466-75, 2014.
In the news: Science Daily, Popular Science, Scientific American, Chemical and Engineering News
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Postdoctoral and graduate work
de Rond T., Peralta-Yahya P., Cheng X., Northen T.R., Keasling J.D. Versatile synthesis of probes for high-throughput enzyme activity screening, Anal Bioanal Chem, 405, 4969-73, 2013.
Romanini D., Peralta-Yahya P., Mondol V., Cornish V.W. A heritable recombination system for synthetic darwinian evolution in yeast, ACS Synth Biol, 1, 602-9, 2012.
Peralta-Yahya P., Zhang F., del Cardayre S.B., Keasling J.D. Microbial engineering for the production of advanced biofuels, Nature, 488, 320-28, 2012.
McAndrew R,P., Peralta-Yahya P., DeGiovanni A., Pereira J.H., Hadi M.Z., Keasling J.D., Adams P.D. Structure of a three-domain sesquiterpene synthase: a prospective target for advanced biofuels production. Structure, 19, 1875-84, 2011.
Peralta-Yahya P., Ouellet M., Chan R., Mukhopadhyay A., Keasling J.D., Lee T.S. Identification and microbial production of a terpene-based advanced biofuel, Nat Commun 2:483, doi: 10.1038/ncomms1494, 2011.
Bokinsky G., Peralta-Yahya P., George A., Holmes B.M., Steen E.J., Dietrich J., Lee T.S., Tullman-Ercek D., Voigt C.A., Simmons B.A., Keasling J.D Synthesis of three advanced biofuels from ionic liquid-pretreated switchgrass using engineered Escherichia coli, Proc Natl Acad Sci USA. 108, 19949-54, 2011.
Pirakitikulr N., Ostrov N., Peralta-Yahya P., Cornish, V.W. PCRless library mutagenesis via oligonucleotide recombination in yeast. Protein Sci, 19, 2336-46, 2010.
Peralta-Yahya P., Keasling J.D. Advanced biofuel production in microbes, Biotechnol J, 5, 147-62, 2010.
Peralta-Yahya P., Carter B.T., Lin H., Tao H., Cornish V.W. High-throughput selection for cellulase catalysts using chemical complementation, J Am Chem Soc, 130, 17446-52, 2008.
Tao H., Peralta-Yahya P., Decatur J., Cornish V.W. Characterization of a new glycosynthase cloned by using chemical complementation, ChemBioChem, 9, 681-4, 2008.
Peralta-Yahya P., Cornish V.W. Bringing the power of genetics to chemistry, in Chemical Biology, S.L. Schreiber, T. Kapoor, G. WEiss, Eds. Wiley-VCH Verlag, 2007.
Tao H., Peralta-Yahya P., Lin H., Cornish V.W., Optimized design and synthesis of chemical dimerizer substrates for detection of glycosynthase activity via chemical complementation, Bioorg Med Chem, 14, 6940-53, 2006.
de Rond T., Peralta-Yahya P., Cheng X., Northen T.R., Keasling J.D. Versatile synthesis of probes for high-throughput enzyme activity screening, Anal Bioanal Chem, 405, 4969-73, 2013.
Romanini D., Peralta-Yahya P., Mondol V., Cornish V.W. A heritable recombination system for synthetic darwinian evolution in yeast, ACS Synth Biol, 1, 602-9, 2012.
Peralta-Yahya P., Zhang F., del Cardayre S.B., Keasling J.D. Microbial engineering for the production of advanced biofuels, Nature, 488, 320-28, 2012.
McAndrew R,P., Peralta-Yahya P., DeGiovanni A., Pereira J.H., Hadi M.Z., Keasling J.D., Adams P.D. Structure of a three-domain sesquiterpene synthase: a prospective target for advanced biofuels production. Structure, 19, 1875-84, 2011.
Peralta-Yahya P., Ouellet M., Chan R., Mukhopadhyay A., Keasling J.D., Lee T.S. Identification and microbial production of a terpene-based advanced biofuel, Nat Commun 2:483, doi: 10.1038/ncomms1494, 2011.
Bokinsky G., Peralta-Yahya P., George A., Holmes B.M., Steen E.J., Dietrich J., Lee T.S., Tullman-Ercek D., Voigt C.A., Simmons B.A., Keasling J.D Synthesis of three advanced biofuels from ionic liquid-pretreated switchgrass using engineered Escherichia coli, Proc Natl Acad Sci USA. 108, 19949-54, 2011.
Pirakitikulr N., Ostrov N., Peralta-Yahya P., Cornish, V.W. PCRless library mutagenesis via oligonucleotide recombination in yeast. Protein Sci, 19, 2336-46, 2010.
Peralta-Yahya P., Keasling J.D. Advanced biofuel production in microbes, Biotechnol J, 5, 147-62, 2010.
Peralta-Yahya P., Carter B.T., Lin H., Tao H., Cornish V.W. High-throughput selection for cellulase catalysts using chemical complementation, J Am Chem Soc, 130, 17446-52, 2008.
Tao H., Peralta-Yahya P., Decatur J., Cornish V.W. Characterization of a new glycosynthase cloned by using chemical complementation, ChemBioChem, 9, 681-4, 2008.
Peralta-Yahya P., Cornish V.W. Bringing the power of genetics to chemistry, in Chemical Biology, S.L. Schreiber, T. Kapoor, G. WEiss, Eds. Wiley-VCH Verlag, 2007.
Tao H., Peralta-Yahya P., Lin H., Cornish V.W., Optimized design and synthesis of chemical dimerizer substrates for detection of glycosynthase activity via chemical complementation, Bioorg Med Chem, 14, 6940-53, 2006.