Peter G. Schultz

Peter G. Schultz (born June 23, 1956) is an American chemist. He is the CEO and Professor of Chemistry at

Much of Schultz's work consists of finding ways to do a great many similar experiments at the same time, on many different compounds. He is one of the leading pioneers in combinatorial chemistry, screenable molecular libraries, and "high-throughput" chemistry. His interests are extremely wide-ranging, with applications in such diverse areas as catalytic mechanisms, cell-specialization and other complex biological processes (normally studied by biologists, not chemists), basic photochemistry, biophysical probes of all stripes from NMR through positron-emission, and solid-state materials science.

Early in his career Schultz showed that the natural molecular diversity of the immune system could be directed to generate catalytic antibodies. This method enabled the subsequent development of many new selective enzyme-like catalysts for reactions ranging from acyl transfer and redox reactions to pericyclic and metalation reactions. Although their catalytic activities are only rarely strong enough to be of practical use, catalytic antibodies have provided important new insights in our understanding of biocatalysis, structural plasticity of proteins, evolution of biochemical function, and the immune system itself.

Schultz then applied molecular diversity—the strategy of creating a large community of different molecules, plus a method for fishing out and identifying the ones that do what you want—to a range of problems in chemistry, biology and materials science. Along with Richard Lerner, he was one of the critical players in the development of phage-display libraries, and surface-library chips. For high-throughput bioassays which require freely soluble test-compounds, he uses microrobotic fluid-manipulation systems, adapted for 1,536-microwell cell-culture plates, to separately treat very small cell colonies with large numbers (hundreds of thousands) of different compounds.^[10]

Using these various high-throughput and combinatorial experimental approaches, Schultz has identified materials with novel optical, electronic, and catalytic properties; also, proteins and small molecules which control important biological processes such as aging, cancer, autoimmunity, and stem-cell differentiation and de-specialization back to pluripotency.

Unnatural amino acids

Schultz has pioneered a method for

More than seventy unnatural amino acids have been genetically encoded in bacteria, yeast, and mammalian cells, including photoreactive, chemically reactive, fluorescent, spin-active, sulfated, pre-phosphorylated, and metal-binding amino acids. This technology allows chemists to probe, and change, the properties of proteins, in vitro or in vivo, by directing novel, lab-synthesized chemical moieties specifically into any chosen site of any protein of interest.

A bacterial organism has been generated which biosynthesizes a novel, previously unnatural amino acid (p-aminophenylalanine) from basic carbon sources and includes this amino acid in its genetic code.^[11][12][13] This is the first example of the creation of an autonomous twenty-one-amino-acid organism.

Unnatural genetic information

Schultz's group has recently created bacteria whose chromosomes include unnatural DNA-bases, and bacteria whose chromosomes are hybrids which include both RNA and DNA.^[14][15]

Origins of mitochondria

In order to probe details of the traditionally accepted hypothesis that mitochondria originated when independent bacteria capable of respiratory (oxygen-dependent) metabolism took up residence inside host cells which had previously only been capable of fermentation (metabolism without using oxygen), and evolved to establish a symbiotic relationship with them,^[16] Schultz's group has created bacteria capable of surviving inside yeast cells and maintaining a symbiotic relationship with the host yeast cells by carrying out reactions which the yeast cells cannot catalyze without the bacteria.^[17] One goal of this work is to culture the yeast-bacteria hybrids and see whether the bacterial genome evolves to increase the mutual benefits of its chemical interactions with the host cells, as has happened with mitochondria over time.^[18]

Commercial activities

He is a founder of Affymax Research Institute, Symyx Technologies, Syrrx, Kalypsys, Phenomix, Ilypsa, Ambrx, and Wildcat Discovery Technologies.^{[citation needed]}

Publications and retractions

Schultz has authored around 500 papers.^[9]

One of his papers in 2013 PNAS about making more stable antibodies was retracted, due to suspect data from co-author Shiladitya Sen:

• Wang, F; Sen, S; Zhang, Y; Ahmad, I; Zhu, X; Wilson, IA; Smider, VV; Magliery, TJ; Schultz, PG (12 March 2013). "Somatic hypermutation maintains antibody thermodynamic stability during affinity maturation". Proceedings of the National Academy of Sciences of the United States of America. 110 (11): 4261–6.
  PMID 28874538
  .

Two papers from his lab published in 2004, one in Science and one in Journal of the American Chemical Society, were retracted in 2009, related to work in the Shultz lab by a postdoc, Zhiwen Zhang, on incorporating non-native glycosylated amino acids into proteins. Had it succeeded, this method could have become an essential tool for investigating the functions of carbohydrate attachments to proteins; however, the work could not be replicated, and when the lab went to find the relevant notebooks, they were missing. In the course of the investigation, Zhang received emails and phone calls blackmailing him, and at one point the person doing this wrote to several institutions and Science saying that he or she was going to commit suicide. The lab eventually identified the problem as a misunderstanding of the function of a key enzyme used in the experiments.[19] The papers were:

• Zhang, Z; Gildersleeve, J; Yang, YY; Xu, R; Loo, JA; Uryu, S; Wong, CH; Schultz, PG (16 January 2004). "A new strategy for the synthesis of glycoproteins". Science. 303 (5656): 371–3.
  PMID 19965450
  .
• Xu, R; Hanson, SR; Zhang, Z; Yang, YY; Schultz, PG; Wong, CH (8 December 2004). "Site-specific incorporation of the mucin-type N-acetylgalactosamine-alpha-O-threonine into protein in Escherichia coli". Journal of the American Chemical Society. 126 (48): 15654–5.
  PMID 19731911
  .

Schultz is a member of the American National Academy of Sciences (1993), the Institute of Medicine of the National Academy of Sciences (1998).^[4]

• 2019 Tetrahedron Prize ^[20]
• 2016 Heinrich Wieland Prize
• 2015 Honorary doctorate from Yale University^[21]
• 2013 The Laureate Chemistry for the Future Solvay Prize^[22]
• 2006 ACS Arthur C. Cope Award
• 2003 Paul Ehrlich and Ludwig Darmstaedter Prize
• 1995 honorary doctorate from Uppsala University, Sweden^[23]
• 1994 Wolf Prize in Chemistry
• 1990 ACS Award in Pure Chemistry
• 1988 NSF Alan T. Waterman Award

References