40.   Patel A, Marquez-Gomez P., Torp L, Gao L, Peralta-Yahya P. Molecular docking reveals key residues for histamine receptor 2 binding site, submitted.

39.   Westenberg R and Peralta-Yahya P. Towards implementation of carbon conservation networks in non-model organisms, submitted.


38.   Patel A and Peralta-Yahya P. Olfactory receptors as an emerging chemical sensing scaffold, Biochemistry, 62, 187-195, 2022.

In this Perspective, we briefly overview recent advances in the biosensing of small molecules. We then look more closely at G protein-coupled receptor (GPCR)-based sensors and consider the chemical sensing capabilities of the largest GPCR subfamily, olfactory receptors (ORs). We examine ORs’ role in nature, their potential as a biomedical target, and their ability to detect compounds not amenable for detection using other biological scaffolds. We conclude by evaluating the current challenges, opportunities, and future applications of GPCR- and OR-based sensors.

37.   Marquez-Gomez P, Kruyer N, Eisen S, Torp L, Howie R, Jones E, France S, Peralta-Yahya P. Discovery of 8-hydroxyquinoline as a histamine receptor 2 blocker scaffold, ACS Synth Biol, 11, 2820-2828, 2022.

Histamine receptor 2 (HRH2) activation results in gastric acid secretion, and HRH2 blockers are used to treat peptic ulcers.  Some HRH2 blockers decomposes to NDMA, a human carcinogen, in the body. We developed a high-throughput  HRH2-based sensor and use it to identify three novel HRH2 blockers, chlorquinaldol, chloroxine, and broxyquinoline. The blockers share an 8-hydroxyquinoline scaffold, which is not found among known HRH2 blockers. This work demonstrates the utility of GPCR-based sensors for rapid drug discovery applications.


36.   Chowdhury S. & Peralta-Yahya P. Two steps to sustainable polymersNat Chem13, 1157-1158, 2021.
35.   Kruyer N., Realff M., Sun W., Genzale, C., Peralta-Yahya P. Designing the bioproduction of Martian rocket propellant via a biotechnology-enabled insitu resource utilization strategyNat Commun12, 6166, 2021.

Mars colonization demands technological advances to enable the return of humans to Earth. Shipping the propellant and oxygen for a return journey is not viable. Considering the gravitational and atmospheric differences between Mars and Earth, we propose bioproduction of a Mars-specific rocket propellant, 2,3-butanediol (2,3-BDO), from CO2, sunlight and water on Mars via a biotechnology-enabled in situ resource utilization strategy.

34.   Kiattisewee C., Dong C., Fontana J., Sugianto W., Peralta-Yahya P., Carothers J., Zalatan, J. Portable bacterial CRISPR transcriptional activation enables metabolic engineering in Pseudomonas putida, Metab Eng, 66, 283-295, 2021.

33.   Yasi E. and Peralta-Yahya P. Screening for serotonin receptor 4 agonist using GPCR-based sensors in yeastMethods in Molecular Biology, 2268, 77-84, 2021.

32.   Kruyer, N., Sugianto W., Tickman B., Alba Burbano, D., Noireaux, V., Carothers, J., Peralta-Yahya P.  Membrane augmented cell-free systems: a new frontier in biotechnology, ACS Synth Biol, 10,670-681, 2021.

Cell-free systems (CFS) have distinct advantages over living organisms in terms of toxicity tolerance and ease of downstream separations processes. However, conventional CFSs lack the ability to synthesize membrane proteins due to a lack of stabilizing interface. Here we review recent advances in membrane augmented CFSs, for the production of membrane proteins, with applications towards high-throughput enzyme screening, complex chemical biosynthesis, enzyme fuel cells, and targeted cell therapeutics using membrane-associated receptor proteins. ​


31.   Kruyer N., Wauldron N., Bommarius A., Peralta-Yahya P. Fully biological production of adipic acid analogs from branched catechols, Scientific Reports, 10, 13367, 2020.

30.   Kruyer N., Wauldron N., Bommarius A., Peralta-Yahya P. Advances in G protein-coupled receptor high-throughput screening, Curr Opin Biotech, 64, 210, 2020.

29.   Kruyer N. and Peralta-Yahya P. Advancing the Potential for the Production of Chemicals from Carbon Dioxide in Escherichia coli, Biochemistry, 59, 731, 2020.


28.  Yasi E, Allen A, Sugianto W, Peralta-Yahya P. Identification of Three Antimicrobials Activating Serotonin Receptor 4 in Colon Cells, ACS Synth Biol, 8, 2710, 2019.

Agonists of the serotonin receptor 4 (5-HTR4) are used to treat irritable bowel syndrome . Here, we developed a 5-HTR4-based sensor capable of testing one compound per second and used it to screen >1,000 chemicals. We identified three antibiotic ligands that result in increased colon cell motility. This assay can be used to screen large pharmaceutical libraries to identify novel treatments for IBS. This work shows that antimicrobials interact not only with the gut microbiota, but also with the human host.

27. 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.

Olfactory receptors are expressed ectopically throughout the body. A key challenge in studying the role of ectopically expressed olfactory receptos (exORs) is the fact that most of them have no known compounds that activate them. We generated sensors for colon exORs  and deorphanized 2 of them. We can now start understanding the role of olfactory receptors in the colon.

26.   Aurand E*, Keasling J, Friedman D, Salis H, Liu C, Peralta-Yahya P, Carothers J, Arkin A, Collins A, Galm U, Cizauskas C, Haynes K, Lu A, Savage D, Annaluru V, Bovenberg R, Carlson P, Contreras L, Freemont P, Hamazato F, Jewett M, Khalil A, Plassmeier J, Roubos H, Sampson J, Wook Chang M
Engineering biology: A research roadmap for the next-generation bioeconomy, Engineering Biology Research Consortium,2019.


25. 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.

Microbial production of chemicals relies on the introduction of enzymes from different organisms into a biotechnology accessible organism, such as Escherichia coli. Often, little attention is paid to the interaction between the heterologous and host enzymes. Here, we optimized the interphase of E. coli‘s acyl carrier protein (ACP) and Acinetobacter baylyi thioesterase to improve medium-chain fatty production.


24.   Sarria S., Kruyer N., Peralta-Yahya P. Microbial synthesis of medium-chain chemicals form renewables, Nature Biotechnology, 35, 1158-1166, 2017.

23.   Ehrenworth A., Claiborne T., Peralta-Yahya P. Medium-throughput screen of microbially produced serotonin via a GPCR-based sensor, Biochemistry, 56, 5471-5475, 2017.

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 enable high-throughput metabolic engineering applications. Here, we engineer a yeast-based serotonin sensor, used it to detect microbially produced serotonin, and validated the assay for medium-throughput screening applications.

22.   Ehrenworth A., Haines M., Wong A., Peralta-Yahya P. Quantifying the efficiency of Saccharomyces cerevisiae translocation tags, Biotech Bioeng, 114, 2628-2636, 2017.

21.   Kruyer N. and Peralta-Yahya P. Metabolic engineering strategies to bio-adipic acid production, Curr Opin Biotechnol, 45, 136-143, 2017.

20.   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,, Health medicinetS

Some pharmaceuticals are obtained via chemical derivatization of plant natural products. Today, plant pathways can be ported to microbes and by combining them with engineered enzymes, modified natural products that more closely resemble pharmaceuticals can be obtained. Here, we analyzed >2,000 FDA approved drugs and proposed pathways and engineered enzymes to produce modified plant alkaloids to accelerate the semi-synthesis of 7 pharmaceuticals currently on the market.


19.   Amit I, Baker D, Barker R, Berger B, Bertozzi C, Bhatia S, Biffi A, Demichelis F, Doudna J, Dowdy SF, Endy D, Helmstaedter M, Junca H, June C, Kamb S, Khvorova A, Kim DH, Kim JS, Krishnan Y, Lakadamyali M, Lappalainen T, Lewin S, Liao J, Loman N, Lundberg E, Lynd L, Martin C, Mellman I, Miyawaki A, Mummery C, Nelson K, Paz J, Peralta-Yahya P, Picotti P, Polyak K, Prather K, Qin J, Quake S, Regev A, Rogers JA, Shetty R, Sommer M, Stevens M, Stolovitzky G, Takahashi M, Tang F, Teichmann S, Torres-Padilla ME, Tripathi L, Vemula P, Verdine G, Vollmer F, Wang J, Ying JY, Zhang F, Zhang T. Voices of biotech. Nat Biotechnol, 34, 270-275, 2016.


18.   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

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.

17.   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

16.   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

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 approaches.  Here, we developed a platform for the generation of G-protein coupled receptor (GPCR)-based sensors in yeast.

15. Voices of chemical biology. Nat Chem Biol. 11, 378-179, 2015.

14.    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


13.   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

Postdoctoral and graduate work

12.   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.

11.   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.

10.   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.

9.   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.

8. 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.

7.   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.

6.   Pirakitikulr N., Ostrov N., Peralta-Yahya P., Cornish, V.W. PCRless library mutagenesis via oligonucleotide recombination in yeast. Protein Sci, 19,
      2336-46, 2010.

5.    Peralta-Yahya P., Keasling J.D. Advanced biofuel production in microbes, Biotechnol J, 5, 147-62, 2010.

4.    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.

3.    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.

2.    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.

1.    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.