Microbiology and Molecular Biology Reviews

A Publication of the American Society for Microbiology

VOLUME 72 ● SEPTEMBER 2008 ● NUMBER 3

CONTENTS/SUMMARIES

Progress in Metabolic Engineering of Saccharomyces cerevisiae. Elke Nevoigt ...... 379–412

Summary: The traditional use of the yeast Saccharomyces cerevisiae in alcoholic fermentation has, over time, resulted in substantial accumulated knowledge concerning genetics, physiology, and biochemistry as well as genetic engineering and fermentation technologies. S. cerevisiae has become a platform organism for developing metabolic engineering strategies, methods, and tools. The current review discusses the relevance of several engineering strategies, such as rational and inverse metabolic engineering, evolutionary engineering, and global transcription machinery engineering, in yeast strain improvement. It also summarizes existing tools for fine-tuning and regulating activities and thus metabolic pathways. Recent examples of yeast metabolic engineering for food, beverage, and industrial biotechnology (bioethanol and bulk and fine chemicals) follow. S. cerevisiae currently enjoys increasing popularity as a production organism in industrial (“white”) biotechnology due to its inherent tolerance of low pH values and high ethanol and inhibitor concentrations and its ability to grow anaerobically. Attention is paid to utilizing lignocellulosic biomass as a potential .

Methods for Sampling of Airborne Viruses. Daniel Verreault, Sylvain Moineau, and Caroline Duchaine ...... 413–444

Summary: To better understand the underlying mechanisms of aerovirology, accurate sampling of airborne viruses is fundamental. The sampling instruments commonly used in aerobiology have also been used to recover viruses suspended in the air. We reviewed over 100 papers to evaluate the methods currently used for viral aerosol sampling. Differentiating infections caused by direct contact from those caused by airborne dissemination can be a very demanding task given the wide variety of sources of viral aerosols. While epidemiological data can help to determine the source of the contamination, direct data obtained from air samples can provide very useful information for risk assessment purposes. Many types of samplers have been used over the years, including liquid impingers, solid impactors, filters, electrostatic precipitators, and many others. The efficiencies of these samplers depend on a variety of environmental and methodological factors that can affect the integrity of the virus structure. The aerodynamic size distribution of the aerosol also has a direct effect on sampler efficiency. Viral aerosols can be studied under controlled laboratory conditions, using biological or nonbiological tracers and surrogate viruses, which are also discussed in this review. Lastly, general recommendations are made regarding future studies on the sampling of airborne viruses.

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Getting a Handle on the Role of Coenzyme M in Alkene Metabolism. Arathi M. Krishnakumar, Darius Sliwa, James A. Endrizzi, Eric S. Boyd, Scott A. Ensign, and John W. Peters ...... 445–456

Summary: Coenzyme M (2-mercaptoethanesulfonate; CoM) is one of several atypical cofactors

discovered in methanogenic archaea which participate in the biological reduction of CO2 to methane. Elegantly simple, CoM, so named for its role as a methyl carrier in all methanogenic archaea, is the smallest known organic . It was thought that this cofactor was used exclusively in methanogenesis until it was recently discovered that CoM is a key cofactor in the pathway of propylene metabolism in the gram-negative soil microorganism Xanthobacter au-

totrophicus Py2. A four-step pathway requiring CoM converts propylene and CO2 to acetoac- etate, which feeds into central metabolism. In this process, CoM is used to activate and convert highly electrophilic epoxypropane, formed from propylene epoxidation, into a nucleophilic species that undergoes carboxylation. The unique properties of CoM provide a chemical handle for orienting compounds for site-specific redox chemistry and stereospecific . The three-dimensional structures of several of the in the pathway of propylene metabolism in defined states have been determined, providing significant insights into both the enzyme mechanisms and the role of CoM in this pathway. These studies provide the structural basis for understanding the efficacy of CoM as a handle to direct organic substrate transformations at the active sites of enzymes.

Cross-Species Virus Transmission and the Emergence of New Epidemic Diseases. Colin R. Parrish, Edward C. Holmes, David M. Morens, Eun-Chung Park, Donald S. Burke, Charles H. Calisher, Catherine A. Laughlin, Linda J. Saif, and Peter Daszak...... 457–470

Summary: Host range is a viral property reflecting natural hosts that are infected either as part of a principal transmission cycle or, less commonly, as “spillover” infections into alternative hosts. Rarely, viruses gain the ability to spread efficiently within a new host that was not previously exposed or susceptible. These transfers involve either increased exposure or the acquisition of variations that allow them to overcome barriers to infection of the new hosts. In these cases, devastating outbreaks can result. Steps involved in transfers of viruses to new hosts include contact between the virus and the host, infection of an initial individual leading to amplification and an outbreak, and the generation within the original or new host of viral variants that have the ability to spread efficiently between individuals in populations of the new host. Here we review what is known about host switching leading to viral emergence from known examples, considering the evolutionary mechanisms, virus-host interactions, host range barriers to infection, and processes that allow efficient host-to-host transmission in the new host population.

Biosynthesis and Functions of Mycothiol, the Unique Protective Thiol of Actinobacteria. Gerald L. Newton, Nancy Buchmeier, and Robert C. Fahey ...... 471–494

Summary: Mycothiol (MSH; AcCys-GlcN-Ins) is the major thiol found in Actinobacteria and has many of the functions of glutathione, which is the dominant thiol in other bacteria and eukaryotes but is absent in Actinobacteria. MSH functions as a protected reserve of cysteine and in the detoxification of alkylating agents, reactive oxygen and nitrogen species, and antibiotics. MSH also acts as a thiol buffer which is important in maintaining the highly reducing envi- ronment within the cell and protecting against disulfide stress. The pathway of MSH biosyn- thesis involves production of GlcNAc-Ins-P by MSH glycosyltransferase (MshA), dephosphor- ylation by the MSH phosphatase MshA2 (not yet identified), deacetylation by MshB to produce GlcN-Ins, linkage to Cys by the MSH MshC, and acetylation by MSH synthase (MshD), yielding MSH. Studies of MSH mutants have shown that the MSH glycosyltransferase MshA and the MSH ligase MshC are required for MSH production, whereas mutants in the MSH deacetylase MshB and the acetyltransferase (MSH synthase) MshD produce some MSH and/or a closely related thiol. Current evidence indicates that MSH biosynthesis is controlled by transcriptional regulation mediated by ␴B and ␴R in Streptomyces coelicolor. Identified en-

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zymes of MSH metabolism include mycothione reductase (disulfide reductase; Mtr), the S- nitrosomycothiol reductase MscR, the MSH S-conjugate amidase Mca, and an MSH-depen- dent maleylpyruvate . Mca cleaves MSH S-conjugates to generate mercapturic acids (AcCySR), excreted from the cell, and GlcN-Ins, used for resynthesis of MSH. The phenotypes of MSH-deficient mutants indicate the occurrence of one or more MSH-dependent S-trans- ferases, peroxidases, and mycoredoxins, which are important targets for future studies. Current evidence suggests that several MSH biosynthetic and metabolic enzymes are potential targets for drugs against tuberculosis. The functions of MSH in antibiotic-producing streptomycetes and in bioremediation are areas for future study.

Candida albicans Cell Wall Proteins. W. LaJean Chaffin ...... 495–544

Summary: The Candida albicans cell wall maintains the structural integrity of the organism in addtion to providing a physical contact interface with the environment. The major components of the cell wall are fibrillar polysaccharides and proteins. The proteins of the cell wall are the focus of this review. Three classes of proteins are present in the candidal cell wall. One group of proteins attach to the cell wall via a glycophosphatidylinositol remnant or by an alkali-labile linkage. A second group of proteins with N-terminal signal sequences but no covalent attach- ment sequences are secreted by the classical secretory pathway. These proteins may end up in the cell wall or in the extracellular space. The third group of proteins lack a secretory signal, and the pathway(s) by which they become associated with the surface is unknown. Potential constituents of the first two classes have been predicted from analysis of genome sequences. Experimental analyses have identified members of all three classes. Some members of each class selected for consideration of confirmed or proposed function, phenotypic analysis of a mutant, and regulation by growth conditions and transcription factors are discussed in more detail.

Convergence of Molecular, Modeling, and Systems Approaches for an Understanding of the Escherichia coli Heat Shock Response. Eric Guisbert, Takashi Yura, Virgil A. Rhodius, and Carol A. Gross . . . 545–554

Summary: The heat shock response (HSR) is a homeostatic response that maintains the proper protein-folding environment in the cell. This response is universal, and many of its components are well conserved from bacteria to humans. In this review, we focus on the regulation of one of the most well-characterized HSRs, that of Escherichia coli. We show that even for this simple model organism, we still do not fully understand the central component of heat shock regula- tion, a chaperone-mediated negative feedback loop. In addition, we review other components that contribute to the regulation of the HSR in E. coli and discuss how these additional components contribute to regulation. Finally, we discuss recent genomic experiments that reveal additional functional aspects of the HSR.

AUTHOR’S CORRECTION

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria. Josef Deutscher, Christof Francke, and Pieter W. Postma ...... 555