More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body to treat severe bacterial infections. To understand the translational potential for AMPs, we analyzed FDA-approved drugs in the FDA drug database. We examined their physicochemical properties, secondary structures, and mechanisms of action, and compared them with the peptides in the AMP database. All FDA-approved AMPs were discovered in Gram-positive soil bacteria, and 98% of known AMPs also come from natural sources (skin secretions of frogs and toxins from different species). However, AMPs can have undesirable properties as drugs, including instability and toxicity. Thus, the design and construction of effective AMPs require an understanding of the mechanisms of known peptides and their effects on the human body. This review provides an overview to guide the development of AMPs that can potentially be used as antimicrobial drugs.

Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures—formed by a single sequence—may be a key feature in preventing bacterial resistance and could explain why sequence–function relationships in AMPs remain elusive.

Background: One route for producing cellulosic biofuels is by the fermentation of lignocellulose-derived sugars generated from a pretreatment that can be effectively coupled with an enzymatic hydrolysis of the plant cell wall. While woody biomass exhibits a number of positive agronomic and logistical attributes, these feedstocks are significantly more recalcitrant to chemical pretreatments than herbaceous feedstocks, requiring higher chemical and energy inputs to achieve high sugar yields from enzymatic hydrolysis. We previously discovered that alkaline hydrogen peroxide (AHP) pretreatment catalyzed by copper(II) 2,2΄-bipyridine complexes significantly improves subsequent enzymatic glucose and xylose release from hybrid poplar heartwood and sapwood relative to uncatalyzed AHP pretreatment at modest reaction conditions (room temperature and atmospheric pressure). In the present work, the reaction conditions for this catalyzed AHP pretreatment were investigated in more detail with the aim of better characterizing the relationship between pretreatment conditions and subsequent enzymatic sugar release.Results: We found that for a wide range of pretreatment conditions, the catalyzed pretreatment resulted in significantly higher glucose and xylose enzymatic hydrolysis yields (as high as 80% for both glucose and xylose) relative to uncatalyzed pretreatment (up to 40% for glucose and 50% for xylose). We identified that the extent of improvement in glucan and xylan yield using this catalyzed pretreatment approach was a function of pretreatment conditions that included H₂O₂loading on biomass, catalyst concentration, solids concentration, and pretreatment duration. Based on these results, several important improvements in pretreatment and hydrolysis conditions were identified that may have a positive economic impact for a process employing a catalyzed oxidative pretreatment. These improvements include identifying that: (1) substantially lower H₂O₂loadings can be used that may result in up to a 50-65% decrease in H₂O₂application (from 100 mg H₂O₂/g biomass to 35–50 mg/g) with only minor losses in glucose and xylose yield, (2) a 60% decrease in the catalyst concentration from 5.0 mM to 2.0 mM (corresponding to a catalyst loading of 25 μmol/g biomass to 10 μmol/g biomass) can be achieved without a subsequent loss in glucose yield, (3) an order of magnitude improvement in the time required for pretreatment (minutes versus hours or days) can be realized using the catalyzed pretreatment approach, and (4) enzyme dosage can be reduced to less than 30 mg protein/g glucan and potentially further with only minor losses in glucose and xylose yields. In addition, we established that the reaction rate is improved in both catalyzed and uncatalyzed AHP pretreatment by increased solids concentrations.Conclusions: This work explored the relationship between reaction conditions impacting a catalyzed oxidative pretreatment of woody biomass and identified that significant decreases in the H₂O₂, catalyst, and enzyme loading on the biomass as well as decreases in the pretreatment time could be realized with only minor losses in the subsequent sugar released enzymatically. Together these changes would have positive implications for the economics of a process based on this pretreatment approach.