Bio

Academic Appointments


Honors & Awards


  • Early Career Independence Award (DP5), NIH (2012-2017)
  • Career Award for Medical Scientists, Burroughs-Wellcome Fund (2012-2017)
  • Medical Scientist Training Program (MSTP), NIH (2001-2008)

Professional Education


  • Residency:Stanford Hospital and Clinics (2011) CA
  • Medical Education:Harvard Medical School (2008) MA
  • MD, Harvard Medical School, Medicine (2008)
  • PhD, Harvard Medical School, Biophysics (2006)
  • BA, Harvard University, Biochemical Sciences (2001)

Research & Scholarship

Current Research and Scholarly Interests


Lab website: http://yehlab.stanford.edu/

The chemistry and biology of the unique plastid organelle, the apicoplast, in malaria parasites

Malaria caused by Plasmodium spp parasites has an enormous disease burden that disproportionately affects the world’s poorest and youngest. New anti-malarials with novel drug mechanisms are desperately needed in the face of existing or emerging drug resistance to all available therapies. Investigation of Plasmodium biology offers both the potential for important biomedical impact and an opportunity to explore fascinating eukaryotic biology. Given the challenges of genetic and other approaches to studying this complex organism, the development of chemical tools will be especially critical in pushing forward basic research.

My research focuses on the apicoplast, a prokaryotically-derived plastid organelle unique to Plasmodium (and other pathogenic Apicomplexa parasites) and a key anti-malarial drug target. My laboratory's goal is to elucidate apicoplast biology, function, and role in pathogenesis with the ultimate goal of realizing the potential of the apicoplast as a therapeutic target. In a major step toward this goal, my previous work has demonstrated that the sole essential function of the apicoplast in blood-stage P. falciparum parasites is the biosynthesis of isoprenoid precursors. As such, I was able to generate parasites completely devoid of this essential organelle but chemically rescued by supplementation of the growth media with isopentenyl pyrophosphate (IPP), the pathway product. Chemical rescue and “apicoplast(-)” parasites are innovative tools for investigating apicoplast biology and for advancing apicoplast-directed drug and vaccine development. Our research takes advantage of these new tools and our newfound understanding of apicoplast function to explore a variety of topics, including protein trafficking to the apicoplast and the protein "prenylome" in Plasmodium. We employ a variety of methods but have a particular focus on the use of chemical tools to overcome the current challenges in studying this organelle. Our exploration of the Plasmodium apicoplast are likely to reveal both unique biology and targets for anti-malarial drug development.

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum PLOS BIOLOGY Yeh, E., DeRisi, J. L. 2011; 9 (8)

    Abstract

    Plasmodium spp parasites harbor an unusual plastid organelle called the apicoplast. Due to its prokaryotic origin and essential function, the apicoplast is a key target for development of new anti-malarials. Over 500 proteins are predicted to localize to this organelle and several prokaryotic biochemical pathways have been annotated, yet the essential role of the apicoplast during human infection remains a mystery. Previous work showed that treatment with fosmidomycin, an inhibitor of non-mevalonate isoprenoid precursor biosynthesis in the apicoplast, inhibits the growth of blood-stage P. falciparum. Herein, we demonstrate that fosmidomycin inhibition can be chemically rescued by supplementation with isopentenyl pyrophosphate (IPP), the pathway product. Surprisingly, IPP supplementation also completely reverses death following treatment with antibiotics that cause loss of the apicoplast. We show that antibiotic-treated parasites rescued with IPP over multiple cycles specifically lose their apicoplast genome and fail to process or localize organelle proteins, rendering them functionally apicoplast-minus. Despite the loss of this essential organelle, these apicoplast-minus auxotrophs can be grown indefinitely in asexual blood stage culture but are entirely dependent on exogenous IPP for survival. These findings indicate that isoprenoid precursor biosynthesis is the only essential function of the apicoplast during blood-stage growth. Moreover, apicoplast-minus P. falciparum strains will be a powerful tool for further investigation of apicoplast biology as well as drug and vaccine development.

    View details for DOI 10.1371/journal.pbio.1001138

    View details for Web of Science ID 000294483000019

    View details for PubMedID 21912516

  • Immediate Incubation Reduces Indeterminate Results for QuantiFERON-TB Gold In-Tube Assay JOURNAL OF CLINICAL MICROBIOLOGY Herrera, V., Yeh, E., Murphy, K., Parsonnet, J., Banaei, N. 2010; 48 (8): 2672-2676

    Abstract

    In vitro gamma interferon release assays (IGRAs) are increasingly used as an alternative to the traditional tuberculin skin test for the diagnosis of latent Mycobacterium tuberculosis infection. Evaluation of the QuantiFERON-TB Gold in-tube assay (QFT-IT) prior to large-scale implementation at the Stanford Hospital and Clinics for a health care worker screening program revealed a critical preanalytical factor affecting the results. We found that incubation delay significantly increased the frequency of indeterminate results. In this study, QFT-IT was performed with samples from healthy volunteers, and replicate tubes were incubated at 37 degrees C either immediately or after a delay at room temperature for 6 and 12 h. No indeterminate results (0/41) were seen when the assay was performed with immediate incubation. Incubation delays of 6 and 12 h yielded indeterminate results at rates of 10% (2/20) (P = 0.10) and 17.1% (7/41) (P = 0.01), respectively. The increased rate of indeterminate results was due to a decrease in the mean values for the mitogen-nil tubes when incubation was delayed for 6 h (P = 0.004) and 12 h (P < 0.001). The rates of concordance of positive or negative results obtained following immediate incubation and following 6- and 12-h delays were 77.8% (14/18) and 79.4% (27/34), respectively. Subsequent implementation of the immediate incubation procedure in our screening program for 14,830 health care workers yielded an indeterminate result rate of 0.36% over a period of 12 months, a significant improvement over the reported rates of 5 to 40% for QFT-IT. We conclude that immediate incubation of QFT-IT tubes is an effective way to minimize indeterminate results. The effect of incubation delay on the accuracy of QFT-IT remains to be determined.

    View details for DOI 10.1128/JCM.00482-10

    View details for Web of Science ID 000280550500002

    View details for PubMedID 20519472

  • Real-Time PCR Testing for mecA Reduces Vancomycin Usage and Length of Hospitalization for Patients Infected with Methicillin-Sensitive Staphylococci JOURNAL OF CLINICAL MICROBIOLOGY Nguyen, D. T., Yeh, E., Perry, S., Luo, R. F., Pinsky, B. A., Lee, B. P., Sisodiya, D., Baron, E. J., Banaei, N. 2010; 48 (3): 785-790

    Abstract

    Nucleic acid amplification tests (NAATs) have revolutionized infectious disease diagnosis, allowing for the rapid and sensitive identification of pathogens in clinical specimens. Real-time PCR testing for the mecA gene (mecA PCR), which confers methicillin resistance in staphylococci, has the added potential to reduce antibiotic usage, improve clinical outcomes, lower health care costs, and avoid emergence of drug resistance. A retrospective study was performed to identify patients infected with methicillin-sensitive staphylococcal isolates who were receiving vancomycin treatment when susceptibility results became available. Vancomycin treatment and length of hospitalization were compared in these patients for a 6-month period before and after implementation of mecA PCR. Among 65 and 94 patients identified before and after mecA PCR, respectively, vancomycin usage (measured in days on therapy) declined from a median of 3 days (range, 1 to 44 days) in the pre-PCR period to 1 day (range, 0 to 18 days) in the post-PCR period (P < 0.0001). In total, 38.5% (25/65) of patients were switched to beta-lactam therapy in the pre-PCR period, compared to 61.7% (58/94) in the post-PCR period (P = 0.004). Patient hospitalization days also declined from a median of 8 days (range, 1 to 47 days) in the pre-PCR period to 5 days (range, 0 to 42 days) in the post-PCR period (P = 0.03). Real-time PCR testing for mecA is an effective tool for reducing vancomycin usage and length of stay of hospitalized patients infected with methicillin-sensitive staphylococci. In the face of ever-rising health care expenditures in the United States, these findings have important implications for improving outcomes and decreasing costs.

    View details for DOI 10.1128/JCM.02150-09

    View details for Web of Science ID 000274996200016

    View details for PubMedID 20071556

  • Preferential Lower Respiratory Tract Infection in Swine-Origin 2009 A(H1N1) Influenza CLINICAL INFECTIOUS DISEASES Yeh, E., Luo, R. F., Dyner, L., Hong, D. K., Banaei, N., Baron, E. J., Pinsky, B. A. 2010; 50 (3): 391-394

    Abstract

    We report a case of 2009 influenza A(H1N1) virus infection in which virus was detected predominantly in specimens from the lower respiratory tract but was absent or at very low levels in nasopharyngeal swab samples. This presentation suggests that, in certain hosts or for particular variants of 2009 A(H1N1) virus, the lower respiratory tract may be the preferred site of infection.

    View details for DOI 10.1086/649875

    View details for Web of Science ID 000273500300014

    View details for PubMedID 20047483

  • Hair Sheep Blood, Citrated or Defibrinated, Fulfills All Requirements of Blood Agar for Diagnostic Microbiology Laboratory Tests PLOS ONE Yeh, E., Pinsky, B. A., Banaei, N., Baron, E. J. 2009; 4 (7)

    Abstract

    Blood agar is used for the identification and antibiotic susceptibility testing of many bacterial pathogens. In the developing world, microbiologists use human blood agar because of the high cost and inhospitable conditions for raising wool sheep or horses to supply blood. Many pathogens either fail to grow entirely or exhibit morphologies and hemolytic patterns on human blood agar that confound colony recognition. Furthermore, human blood can be hazardous to handle due to HIV and hepatitis. This study investigated whether blood from hair sheep, a hardy, low-maintenance variety of sheep adapted for hot climates, was suitable for routine clinical microbiology studies.Hair sheep blood obtained by jugular venipuncture was anticoagulated by either manual defibrination or collection in human blood bank bags containing citrate-phosphate-dextrose. Trypticase soy 5% blood agar was made from both forms of hair sheep blood and commercial defibrinated wool sheep blood. Growth characteristics, colony morphologies, and hemolytic patterns of selected human pathogens, including several streptococcal species, were evaluated. Specialized identification tests, including CAMP test, reverse CAMP test, and satellite colony formation with Haemophilus influenzae and Abiotrophia defectiva were also performed. Mueller-Hinton blood agar plates prepared from the three blood types were compared in antibiotic susceptibility tests by disk diffusion and E-test.The results of all studies showed that blood agar prepared from citrated hair sheep blood is suitable for microbiological tests used in routine identification and susceptibility profiling of human pathogens. The validation of citrated hair sheep blood eliminates the labor-intensive and equipment-requiring process of manual defibrination. Use of hair sheep blood, in lieu of human blood currently used by many developing world laboratories and as an alternative to cost-prohibitive commercial sheep blood, offers the opportunity to dramatically improve the safety and accuracy of laboratory diagnosis of pathogenic bacteria in resource-poor countries.

    View details for DOI 10.1371/journal.pone.0006141

    View details for Web of Science ID 000267806300010

    View details for PubMedID 19578541

  • Chlorination by a long-lived intermediate in the mechanism of flavin-dependent halogenases BIOCHEMISTRY Yeh, E., Blasiak, L. C., Koglin, A., Drennan, C. L., Walsh, C. T. 2007; 46 (5): 1284-1292

    Abstract

    The flavin-dependent halogenase RebH catalyzes the formation of 7-chlorotryptophan as the initial step in the biosynthesis of antitumor agent rebeccamycin. The reaction of FADH2, Cl-, and O2 in the active site generates the powerful oxidant HOCl, which was presumed to carry out the chlorination reaction. Herein, we demonstrate the formation of a long-lived chlorinating intermediate (t1/2 = 63 h at 4 degrees C) when RebH, FADH2, Cl-, and O2 react in the absence of substrate tryptophan. This intermediate remained on the enzyme after removal of FAD and transferred chlorine to tryptophan with kinetically competent rates. The identity of this intermediate is suggested by the X-ray crystal structure of RebH, which revealed an active site Lys79 located in a central position between flavin and tryptophan binding sites and just 4.1 A above C7 of tryptophan. The chlorinating species is proposed to be a Lys-epsilonNH-Cl (lysine chloramine) from reaction of enzyme-generated HOCl with the active site Lys79. This covalent enzyme chloramine likely plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes.

    View details for DOI 10.1021/bi0621213

    View details for Web of Science ID 000243839500016

    View details for PubMedID 17260957

  • Characterization of the aminocarboxycyclopropane-forming enzyme CmaC BIOCHEMISTRY Kelly, W. L., Boyne, M. T., Yeh, E., Vosburg, D. A., Galonic, D. P., Kelleher, N. L., Walsh, C. T. 2007; 46 (2): 359-368

    Abstract

    The biosynthesis of the coronamic acid fragment of the pseudomonal phytotoxin coronatine involves construction of the cyclopropane ring from a gamma-chloro-L-allo-Ile intermediate while covalently tethered as a phosphopantetheinyl thioester to the carrier protein CmaD. The cyclopropane-forming catalyst is CmaC, catalyzing an intramolecular displacement of the gamma-Cl group by the alpha carbon. CmaC can be isolated as a Zn2+ protein with about 10-fold higher activity over the apo form. CmaC will not cyclize free gamma-chloro amino acids or their S-N-acetylcysteamine (NAC) thioester derivatives but will recognize some other carrier protein scaffolds. Turnover numbers of 5 min-1 are observed for Zn-CmaC, acting on gamma-chloro-L-aminobutyryl-S-CmaD, generating 1-aminocyclopropane-1-carbonyl (ACC)-S-CmaD. Products were detected either while still tethered to the phosphopantetheinyl prosthetic arm by mass spectrometry or after thioesterase-mediated release and derivatization of the free amino acid. In D2O, CmaC catalyzed exchange of one deuterium into the aminobutyryl moiety of the gamma-Cl-aminoacyl-S-CmaD, whereas the product ACC-S-CmaD lacked the deuterium, consistent with a competition for a gamma-Cl-aminobutyryl alpha-carbanion between reprotonation and cyclization. CmaC-mediated cyclization yielded solely ACC, resulting from C-C bond formation and no azetidine carboxylate from an alternate N-C cyclization. CmaC could cyclize gamma,gamma-dichloroaminobutyryl to the Cl-ACC product but did not cyclize delta- or epsilon-chloroaminoacyl-S-CmaD substrates.

    View details for DOI 10.1021/bi061930j

    View details for Web of Science ID 000243337200004

    View details for PubMedID 17209546

  • Enzymatic generation of the antimetabolite gamma,gamma-dichloroaminobutyrate by NRPS and mononuclear iron halogenase action in a streptomycete CHEMISTRY & BIOLOGY Ueki, M., Galonic, D. P., Vaillancourt, F. H., Garneau-Tsodikova, S., Yeh, E., Vosburg, D. A., Schroeder, F. C., Osada, H., Walsh, C. T. 2006; 13 (11): 1183-1191

    Abstract

    Four adjacent open reading frames, cytC1-C4, were cloned from a cytotrienin-producing strain of a Streptomyces sp. by using primers derived from the conserved region of a gene encoding a nonheme iron halogenase, CmaB, in coronamic acid biosynthesis. CytC1-3 were active after expression in Escherichia coli, and CytC4 was active after expression in Pseudomonas putida. CytC1, a relatively promiscuous adenylation enzyme, installs the aminoacyl moieties on the phosphopantetheinyl arm of the holo carrier protein CytC2. CytC3 is a nonheme iron halogenase that will generate both gamma-chloro- and gamma,gamma-dichloroaminobutyryl-S-CytC2 from aminobutyryl-S-CytC2. CytC4, a thioesterase, hydrolytically releases the dichloroaminobutyrate, a known streptomycete antibiotic. Thus, this short four-protein pathway is likely the biosynthetic source of this amino acid antimetabolite. This four-enzyme system analogously converts the proS-methyl group of valine to the dichloromethyl product regio- and stereospecifically.

    View details for DOI 10.1016/j.chembiol.2006.09.012

    View details for Web of Science ID 000242418400010

    View details for PubMedID 17114000

  • Nature's inventory of halogenation catalysts: Oxidative strategies predominate CHEMICAL REVIEWS Vaillancourt, F. H., Yeh, E., Vosburg, D. A., Garneau-Tsodikova, S., Walsh, C. T. 2006; 106 (8): 3364-3378

    View details for DOI 10.1021/cr050313i

    View details for Web of Science ID 000239624000018

    View details for PubMedID 16895332

  • Flavin redox chemistry precedes substrate chlorination during the reaction of the flavin-dependent halogenase RebH BIOCHEMISTRY Yeh, E., Cole, L. J., Barr, E. W., Bollinger, J. M., Ballou, D. P., Walsh, C. T. 2006; 45 (25): 7904-7912

    Abstract

    The flavin-dependent halogenase RebH catalyzes chlorination at the C7 position of tryptophan as the initial step in the biosynthesis of the chemotherapeutic agent rebeccamycin. The reaction requires reduced FADH(2) (provided by a partner flavin reductase), chloride ion, and oxygen as cosubstrates. Given the similarity of its sequence to those of flavoprotein monooxygenases and their common cosubstrate requirements, the reaction of FADH(2) and O(2) in the halogenase active site was presumed to form the typical FAD(C4a)-OOH intermediate observed in monooxygenase reactions. By using stopped-flow spectroscopy, formation of a FAD(C4a)-OOH intermediate was detected during the RebH reaction. This intermediate decayed to yield a FAD(C4a)-OH intermediate. The order of addition of FADH(2) and O(2) was critical for accumulation of the FAD(C4a)-OOH intermediate and for subsequent product formation, indicating that conformational dynamics may be important for protection of labile intermediates formed during the reaction. Formation of flavin intermediates did not require tryptophan, nor were their rates of formation affected by the presence of tryptophan, suggesting that tryptophan likely does not react directly with any flavin intermediates. Furthermore, although final oxidation to FAD occurred with a rate constant of 0.12 s(-)(1), quenched-flow kinetic data showed that the rate constant for 7-chlorotryptophan formation was 0.05 s(-)(1) at 25 degrees C. The kinetic analysis establishes that substrate chlorination occurs after completion of flavin redox reactions. These findings are consistent with a mechanism whereby hypochlorite is generated in the RebH active site from the reaction of FADH(2), chloride ion, and O(2).

    View details for DOI 10.1021/bi060607d

    View details for Web of Science ID 000238386300024

    View details for PubMedID 16784243

  • Dichlorination of a pyrrolyl-S-carrier protein by FADH(2)-dependent halogenase PltA during pyoluteorin biosynthesis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dorrestein, P. C., Yeh, E., Garneau-Tsodikova, S., Kelleher, N. L., Walsh, C. T. 2005; 102 (39): 13843-13848

    Abstract

    The antifungal natural product pyoluteorin contains a 4,5-dichloropyrrole moiety. The timing of dichlorination in the heteroaromatic ring is now shown to occur after proline is tethered by thioester linkage to the carrier protein PltL and enzymatically desaturated to the pyrrolyl-S-PltL. Surprisingly, the FADH2-dependent halogenase PltA catalyzes chlorination at both positions of the ring, generating the 5-chloropyrrolyl-S-PltL intermediate and then the 4,5-dichloropyrrolyl-S-PltL product. PltA activity strictly depends on a heterologous flavin reductase that uses NAD(P)H to produce FADH2. Electrospray ionization-Fourier transform MS detected five covalent intermediates attached to the 11-kDa carrier protein PltL. Tandem MS localized the site of covalent modification on the carrier protein scaffold. HPLC analysis of the hydrolyzed products was consistent with the regiospecific chlorination at position 5 and then position 4 of the heteroaromatic ring. A mechanism for dichlorination is proposed involving formation of a FAD-4a-OCl intermediate for capture by the electron-rich C4 and C5 of the heteroaromatic pyrrole moiety.

    View details for DOI 10.1073/pnas.0506964102

    View details for Web of Science ID 000232231900026

    View details for PubMedID 16162666

  • Cryptic chlorination by a non-haem iron enzyme during cyclopropyl amino acid biosynthesis NATURE Vaillancourt, F. H., Yeh, E., Vosburg, D. A., O'Connor, S. E., Walsh, C. T. 2005; 436 (7054): 1191-1194

    Abstract

    Enzymatic incorporation of chlorine, bromine or iodine atoms occurs during the biosynthesis of more than 4,000 natural products. Halogenation can have significant consequences for the bioactivity of these products so there is great interest in understanding the biological catalysts that perform these reactions. Enzymes that halogenate unactivated aliphatic groups have not previously been characterized. Here we report the activity of five proteins-CmaA, CmaB, CmaC, CmaD and CmaE-in the construction of coronamic acid (CMA; 1-amino-1-carboxy-2-ethylcyclopropane), a constituent of the phytotoxin coronatine synthesized by the phytopathogenic bacterium Pseudomonas syringae. CMA derives from l-allo-isoleucine, which is covalently attached to CmaD through the actions of CmaA, a non-ribosomal peptide synthetase module, and CmaE, an unusual acyltransferase. We show that CmaB, a member of the non-haem Fe(2+), alpha-ketoglutarate-dependent enzyme superfamily, is the first of its class to show halogenase activity, chlorinating the gamma-position of l-allo-isoleucine. Another previously undescribed enzyme, CmaC, catalyses the formation of the cyclopropyl ring from the gamma-Cl-l-allo-isoleucine product of the CmaB reaction. Together, CmaB and CmaC execute gamma-halogenation followed by intramolecular gamma-elimination, in which biological chlorination is a cryptic strategy for cyclopropyl ring formation.

    View details for DOI 10.1038/nature03797

    View details for Web of Science ID 000231416600053

    View details for PubMedID 16121186

  • Robust in vitro activity of RebF and RebH, a two-component reductase/halogenase, generating 7-chlorotryptophan during rebeccamycin biosynthesis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Yeh, E., Garneau, S., Walsh, C. T. 2005; 102 (11): 3960-3965

    Abstract

    The indolocarbazole antitumor agent rebeccamycin is modified by chlorine atoms on each of two indole moieties of the aglycone scaffold. These halogens are incorporated during the initial step of its biosynthesis from conversion of L-Trp to 7-chlorotryptophan. Two genes in the biosynthetic cluster, rebF and rebH, are predicted to encode the flavin reductase and halogenase components of an FADH2-dependent halogenase, a class of enzymes involved in the biosynthesis of numerous halogenated natural products. Here, we report that, in the presence of O2, chloride ion, and L-Trp as cosubstrates, purified RebH displays robust regiospecific halogenating activity to generate 7-chlorotryptophan over at least 50 catalytic cycles. Halogenation by RebH required the addition of RebF, which catalyzes the NADH-dependent reduction of FAD to provide FADH2 for the halogenase. Maximal rates were achieved at a RebF/RebH ratio of 3:1. In air-saturated solutions, a k(cat) of 1.4 min(-1) was observed for the RebF/RebH system but increased at least 10-fold in low-pO2 conditions. RebH was also able to use bromide ions to generate monobrominated Trp. The demonstration of robust chlorinating activity by RebF/RebH sets up this system for the probing of mechanistic questions regarding this intriguing class of enzymes.

    View details for DOI 10.1073/pnas.0500755102

    View details for Web of Science ID 000227731000015

    View details for PubMedID 15743914

  • Enhanced macrocyclizing activity of the thioesterase from tyrocidine synthetase in presence of nonionic detergent CHEMISTRY & BIOLOGY Yeh, E., Lin, H. N., Clugston, S. L., Kohli, R. M., Walsh, C. T. 2004; 11 (11): 1573-1582

    Abstract

    Macrocyclization carried out by thioesterase domains of multimodular nonribosomal peptide synthetases (NRPSs) is a key step in the biosynthesis of many biologically active peptides. The thioesterase excised from tyrocidine synthetase is a versatile macrocyclization catalyst and a useful tool for chemoenzymatic synthesis of diverse cyclic peptides. However, its utility is limited by its short lifetime of catalytic activity as well as significant flux of the acyl-enzyme intermediate to hydrolysis. The addition of Brij 58, a nonionic detergent, above the critical micelle concentration, has dramatic effects on enzyme activity: catalytic activity is extended to >60 min and the rate of cyclization (but not hydrolysis) increases 6-fold, resulting in a net 150- to 300-fold increase in cyclic product yields. This enhanced activity allowed enzymatic macrocyclization of a solid phase library of tyrocidine decapeptides to identify acceptable substitutions at the Orn9 position which had previously been inaccessible for diversification.

    View details for DOI 10.1016/j.chembiol.2004.09.003

    View details for Web of Science ID 000225613800016

    View details for PubMedID 15556008

  • Type II thioesterase restores activity of a NRPS module stalled with an aminoacyl-S-enzyme that cannot be elongated CHEMBIOCHEM Yeh, E., Kohli, R. M., Bruner, S. D., Walsh, C. T. 2004; 5 (9): 1290-1293

    View details for DOI 10.1002/cbic.200400077

    View details for Web of Science ID 000223811800020

    View details for PubMedID 15368584

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