Питер Г. Шулц: Пионер биосинтетической химии и расширения генетического кода

American biosynthetic chemist

Peter G. Schultz (born June 23, 1956) is an American chemist. He is the CEO and Professor of Chemistry at The Scripps Research Institute, the founder and former director of GNF, and the founding director of the California Institute for Biomedical Research (Calibr), established in 2012. In August 2014, Nature Biotechnology ranked Schultz the #1 top translational researcher in 2013.

Schultz completed his undergraduate degree at Caltech in 1979 and continued there for his doctoral degree (in 1984) with Peter Dervan. His thesis work focused on the generation and characterization of 1,1 diazenes and the generation of sequence selective polypyrrole DNA binding/cleaving molecules. He then spent a year at the Massachusetts Institute of Technology with Christopher Walsh before joining the chemistry faculty at the University of California, Berkeley. He became a Principal Investigator of Lawrence Berkeley National Laboratory in 1985 and an investigator of the Howard Hughes Medical Institute in 1994. In 1999 Schultz moved to The Scripps Research Institute and also became founding Director of the Genomics Institute of the Novartis Research Foundation (GNF), which was initiated purely as a genomic research outlet of Novartis, but which grew during Schultz's tenure to include a significant drug discovery effort and more than triple the number of intended employees (currently over 500 people). In March 2010, he left GNF to return to the non profit sector and founded the California Institute for Biomedical Research (Calibr) in March 2012. He has trained over 300 graduate students and postdoctoral fellows, many of whom are on the faculties of major research universities. 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.

Schultz has pioneered a method for adding new building blocks, beyond the common twenty amino acids, to the genetic codes of prokaryotic and eukaryotic organisms. This is accomplished by screening libraries of mutant amino acyl tRNA synthetases for mutants which charge nonsense codon tRNAs with the desired unnatural amino acid. The organism which expresses such a synthetase can then be genetically programmed to incorporate the unnatural amino acid into a desired protein in the usual way, with the nonsense codon now coding for the unnatural amino acid. Normally, the unnatural amino acid itself must be synthesized in the lab and supplied to the organism by adding it to the organism's growth medium. The unnatural amino acid must also be able to pass through the organism's cell membrane into the interior of the organism. 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. This is the first example of the creation of an autonomous twenty one amino acid organism.

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.

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, 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. 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.

He is a founder of Affymax Research Institute, Symyx Technologies, Syrrx, Kalypsys, Phenomix, Ilypsa, Ambrx, and Wildcat Discovery Technologies.