Abstract：
:Although random mutagenesis and screening and evolutionary engineering have long been the gold standards for strain improvement in industry, the development of more sophisticated recombinant DNA tools has led to the introduction of alternate methods for engineering strain diversity. Here, we summarize several combinatorial cell optimization methods developed in recent years, many of which are more amenable to phenotypic transfer and more efficient in probing greater dimensions of the available phenotypic space. They include tools that enable the fine-tuning of pathway expression (synthetic promoter libraries, tunable intergenic regions (TIGRs)), methods for generating randomized knockout and overexpression libraries, and more global techniques (artificial transcription factor engineering, global transcription machinery engineering, ribosome engineering, and genome shuffling) for eliciting complex, multigenic cellular properties.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Santos CN,Stephanopoulos Gdoi
10.1016/j.cbpa.2008.01.017subject
Has Abstractpub_date
2008-04-01 00:00:00pages
168-76issue
2eissn
1367-5931issn
1879-0402pii
S1367-5931(08)00007-0journal_volume
12pub_type
杂志文章,评审abstract：:Numerous developments in useful linkers are closely related with the advances in solid-phase organic synthesis. These linkers allow facile attachment functionalization and release molecules of interest. Designing a new anchoring group can be essential for synthesis success, especially for small molecules on solid supp...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.04.004
更新日期：2004-06-01 00:00:00
abstract：:Some therapeutic monoclonal antibodies function by focusing the killing power of the immune system on particular cellular targets, a process known as antibody-dependent cell-mediated cytotoxicity (ADCC). There is considerable interest in developing small-molecule therapeutics that utilize this mechanism of action and ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.07.002
更新日期：2010-12-01 00:00:00
abstract：:Peptides that recognize specific cell types promise to be valuable tools both in research and clinical applications. Cell-specific peptides can be useful as drug delivery vehicles, diagnostic agents, affinity reagents for cell purification, gene therapy delivery agents, and research tools to probe the nature of a cell...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00045-9
更新日期：2000-02-01 00:00:00
abstract：:The global nitrogen cycle is the process in which different forms of environmental N are interconverted by microorganisms either for assimilation into biomass or in respiratory energy-generating pathways. This short review highlights developments over the last 5 years in our understanding of functionality of nitrogena...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.02.009
更新日期：2016-04-01 00:00:00
abstract：:Protein engineering over the past four years has made rhodopsin-based genetically encoded voltage indicators a leading candidate to achieve the task of reporting action potentials from a population of genetically targeted neurons in vivo. Rational design and large-scale screening efforts have steadily improved the dyn...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.05.006
更新日期：2015-08-01 00:00:00
abstract：:RNA plays an essential cellular role in nearly every aspect of the transmission and expression of genetic information, including regulatory roles that have significance for cellular development. Access to RNA bearing synthetic modifications has allowed biological chemists to probe deep into the inner workings of cellu...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.10.009
更新日期：2005-12-01 00:00:00
abstract：:The metal-free hydrogenase from methanogenic archaea (Hmd) is a unique enzyme: it catalyzes the reaction of its substrate, methenyl-tetrahydromethanopterin, with molecular hydrogen without the aid of a transition metal. In other words, Hmd is currently the only example of a purely organic hydrogenation catalyst. Recen...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00245-3
更新日期：2001-10-01 00:00:00
abstract：:Chemical manipulation of natural, unengineered proteins is a daunting challenge which tests the limits of reaction design. By combining transition-metal or other catalysts with molecular recognition ideas, it is possible to achieve site-selective protein reactivity without the need for engineered recognition sequences...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.12.017
更新日期：2015-04-01 00:00:00
abstract：:Fragment-based screening has now become an established method for the generation of lead molecules against therapeutic targets. Fragment molecules are simple, low molecular-weight compounds with few chemical functionalities. These characteristics lead to high hit rates for fragment screening as compared to the more cl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.02.020
更新日期：2011-08-01 00:00:00
abstract：:Metal ions are known to act as catalytic centres in metallo-enzymes. On the other hand, low-molecular-weight metal complexes are widely used as catalysts in chemical systems. However, small catalysts do not have a large protein ligand to provide substrate selectivity and minimize catalyst poisoning. Despite the challe...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.01.024
更新日期：2015-04-01 00:00:00
abstract：:Recent advances in the development of the phosphorescent Ir(III) complexes have made it possible to implement the phosphorescence modality in bioimaging applications. A variety of phosphorescent Ir(III) complexes have been synthesized and assessed in the context of in vitro and in vivo imaging, especially in subcellul...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2013.05.023
更新日期：2013-08-01 00:00:00
abstract：:Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.07.008
更新日期：2017-10-01 00:00:00
abstract：:The introduction of fluorine atoms into organic molecules has received considerable attention as these organofluorines have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of synthetic C-F forming methodologies, selective fluorination is stil...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.01.004
更新日期：2020-04-01 00:00:00
abstract：:Inhibition of the steroid 5alpha-reductases shows promise in the treatment of a number of androgen-dependent disorders, such as benign prostatic hyperplasia, male pattern baldness, and acne. The design of potent and isozyme-selective inhibitors has provided biologists and clinicians with important tools for elucidatin...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80017-8
更新日期：1997-08-01 00:00:00
abstract：:Recent developments in the prediction of toxicity from chemical structure have been reviewed. Attention has been drawn to some of the problems that can be encountered in the area of predictive toxicology, including the need for a multi-disciplinary approach and the need to address mechanisms of action. Progress has be...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00218-0
更新日期：2001-08-01 00:00:00
abstract：:NMR, already some 50 years old, has long been an invaluable analytical method in industry for verification of chemical synthesis and compound characterisation. The range of molecular information accessible through NMR, however, offers a far larger horizon of applications. Of these, ligand screening by NMR has emerged ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00204-0
更新日期：2001-06-01 00:00:00
abstract：:In the past five to ten years, it has become increasingly apparent that the function of Fe-S clusters is not limited to electron transfer, a function implicit in their discovery. We now know that the vulnerability of these structures to oxidative destruction is used by nature in sensing O2, iron, and possibly also nit...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/S1367-5931(99)80027-1
更新日期：1999-04-01 00:00:00
abstract：:Study of protein adsorption to solid surfaces continues to be substantial because of its role in cellular responses to biomaterials, interest in molecular aspects such as conformation and orientation, new methods for making protein repellent surfaces, and new application areas such as nanoparticles and microfluidics. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.04.016
更新日期：2011-10-01 00:00:00
abstract：:The site specific, co-translational introduction of unnatural amino acids into proteins produced in cells has been facilitated by the development of the pyrrolysyl-tRNA synthetase/tRNACUA pair. This pair can now be used to direct the site-specific incorporation of designer amino acids in E. coli, yeast, mammalian cell...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.07.001
更新日期：2014-08-01 00:00:00
abstract：:Peptide natural products (PNPs) represent a unique class of compounds known for their fascinating structural motifs with important biological activities. Lately, PNPs have garnered a lot of interest for their application in drug discovery. Nevertheless, lack of diversity oriented synthetic/biosynthetic platforms to ge...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.06.006
更新日期：2016-10-01 00:00:00
abstract：:Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction of protein lipidation is also implicated in many pathological states, yet its systematic analysis presents significant challenges. Thanks to i...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.10.002
更新日期：2020-11-19 00:00:00
abstract：:Great progress has been made in expanding the repertoire of genetically encoded fluorescent sensors for monitoring intracellular transition metals (TMs). This powerful toolkit permits dynamic and non-invasive detection of TMs with high spatial-temporal resolution, which enables us to better understand the roles of TM ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.12.002
更新日期：2018-04-01 00:00:00
abstract：:The notorious difficulty of elucidating structures of membrane transporters by crystallography has long prevented our understanding of active transport mechanism coupled with ion/proton transport. The determination of the first crystal structure of the drug/H+ antiporter AcrB was a breakthrough for structure-based und...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.08.014
更新日期：2003-10-01 00:00:00
abstract：:Fourier transform infrared (FTIR) spectroscopy has long been a powerful tool for structural analysis of membrane proteins. However, because of difficulties in resolving contributions from individual residues, most of the derived measurements tend to yield average properties for the system under study. Isotope editing,...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.08.013
更新日期：2006-10-01 00:00:00
abstract：:Lysine acetylation has emerged as a key post-translational modification found at many sites throughout the cell. It plays an important role in epigenetic processes, and more generally in the regulation of protein stability and interactions. Acetyl groups are installed by lysine acetyltransferases and removed by lysine...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2018.06.015
更新日期：2018-08-01 00:00:00
abstract：:The fermentation of synthesis gas (including carbon monoxide, carbon dioxide, and hydrogen) with anaerobic acetogens is an established biotechnological process that has recently been transferred to a commercial scale. The natural product spectrum of acetogens is natively restricted to acetate, ethanol, and 2,3-butaned...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.003
更新日期：2017-12-01 00:00:00
abstract：:A number of nitrile-related enzymes have been screened over the past year for use in synthetic applications. There have also been significant advances in our understanding of the structures and modes of regulation of metal-containing nitrile hydratases. Enzyme structural characterization has provided new insights into...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)00058-7
更新日期：2000-02-01 00:00:00
abstract：:Recent advances in -omic profiling technologies have ushered in an era where we no longer want to merely measure the presence or absence of a biomolecule of interest, but instead hope to understand its function and interactions within larger signaling networks. Here, we review several emerging proteomic technologies c...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.02.001
更新日期：2020-02-01 00:00:00
abstract：:Synthetic biology offers a bottom-up engineering approach that intends to understand complex systems via design-build-test cycles. Embryonic development comprises complex processes that originate at the level of gene regulatory networks in a cell and emerge into collective cellular behaviors with multicellular forms a...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2019.04.006
更新日期：2019-10-01 00:00:00
abstract：:Although new detection screening methods must still be developed, the actual main limitation in combinatorial chemistry seems to be the diversity of ligands that can be generated in terms of real structural and chemical diversity. Thus, there is a strong interest for the development of different strategies for the par...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.04.006
更新日期：2004-06-01 00:00:00
