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Species distribution modelling is a technique used in ecology and conservation biology to predict the potential distribution of a species based on environmental variables. It involves analysing the relationship between known occurrences of a species and environmental factors to create a model that can then predict where the species might be found. Amblypodia anita is a species of butterfly belonging to the family Lycaenidae, found primarily in Southeast Asia. Information about the specific conservation status of Amblypodia anita varies based on regional assessments. However, like many butterfly species, threats such as habitat destruction, climate change, and habitat fragmentation pose risks to its populations. The study trained a model on the current distribution of Amblypodia anita in West Bengal, India, using MaxEnt modelling. Fourteen environmental variables were selected to build the model. Results suggest that cultivated and managed vegetation (36.5%) serves as the most important variable. Running the developed model, the team was then able to predict that 6619 km2 of suitable habitat for Amblypodia anita butterflies exists in West Bengal, India. This analytical approach to area-based conservation may be used in conservation management and focuses on protecting specific geographical areas to preserve biodiversity, ecosystems, and natural resources. [ABSTRACT FROM AUTHOR]

Birds play various crucial roles in the ecosystem including pollination, seed dispersal, and pest control. Assemblages of bird species in a particular landscape are useful predictors in various ecosystem services, this is evident from studies of forest bird assemblages, aquatic bodies and agro ecosystems. For developing conservation strategies, information on bird species assemblages in a particular geographical area is important. Diversity in aquatic ecosystem support a diversity of water bird species. In the present study, around 45 bird species were recorded in 21 aquatic bodies in Bankura, West Bengal, India, in which two species, namely, Leptoptilos javanicus and Aythya ferina declared 'Vulnerable' and three species such as Mareca falcata, Threskiornis melanocephalus, and Limosa limosa considered as 'Near Threatened' according to the IUCN Red list. Dendrocygna javanica and Nettapus coromandelianus were found to be the most abundant. In those 21 study areas, site6 has the highest species richness and site2 has the lowest. The dominance index was highest for site2 and lowest for site6. Pielou's index of evenness was highest for site20. The rarefaction curve showed species abundance was highest for site1. Classical cluster analysis for species abundance showsthat site20, site21, site3, site8, site4, site19, site5, site14, site12, site15, site7, site 10 site11, and site13 are closely related. This paper is aimed to generate interest among people to conserve aquatic birds and their habitats and to document baseline information for further study. [ABSTRACT FROM AUTHOR]

Lanthipeptides are natural products that belong to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs). They contain characteristic lanthionine (Lan) or methyllanthionine (MeLan) structures that contribute to their diverse biological activities. Despite its structurally diverse set of 30 substrates, the highly substrate-tolerant lanthipeptide synthetase ProcM is shown to display high selectivity for formation of a single product from selected substrates. Mutation of the active site zinc ligands to alanine or the unique zinc ligand Cys971 to histidine resulted in a decrease of the cyclization rate, especially for the second cyclization of the substrates ProcA1.1, ProcA2.8, and ProcA3.3. Surprisingly, for ProcA3.3 these mutations also altered the regioselectivity of cyclization resulting in a new major product. ProcM was not able to correct the ring topology of incorrectly cyclized intermediates and products, suggesting that thermodynamic control is not operational. Collectively, the data in this study suggest that the high regioselectivity of product formation is governed by the selectivity of the initially formed ring. [ABSTRACT FROM AUTHOR]

Lanthipeptides are a class of post-translationally modified peptide natural products. They contain lanthionine (Lan) and methyllanthionine (MeLan) residues, which generate cross-links and endow the peptides with various biological activities. The mechanism of a highly substrate-tolerant lanthipeptide synthetase, ProcM, was investigated herein. We report a hybrid ligation strategy to prepare a series of substrate analogues designed to address a number of mechanistic questions regarding catalysis by ProcM. The method utilizes expressed protein ligation to generate a C-terminal thioester of the leader peptide of ProcA, the substrate of ProcM. This thioester was ligated with a cysteine derivative that resulted in an alkyne at the C-terminus of the leader peptide. This alkyne in turn was used to conjugate the leader peptides to a variety of synthetic peptides by copper-catalyzed azide—alkyne cycloaddition. Using deuterium-labeled Ser and Thr in the substrate analogues thus prepared, dehydration by ProcM was established to occur from C-to-N-terminus for two different substrates. Cyclization also occurred with a specific order, which depended on the sequence of the substrate peptides. Furthermore, using orthogonal cysteine side-chain protection in the two semisynthetic peptide substrates, we were able to rule out spontaneous non-enzymatic cyclization events to explain the very high substrate tolerance of ProcM. Finally, the enzyme was capable of exchanging protons at the a-carbon of MeLan, suggesting that ring formation could be reversible. These findings are discussed in the context of the mechanism of the substrate-tolerant ProcM, which may aid future efforts in lanthipeptide engineering. [ABSTRACT FROM AUTHOR]

Natural product discovery has been boosted by genome mining approaches, but compound purification is often still challenging. We report an enzymatic strategy for 'stable isotope labeling of phosphonates in extract' (SILPE) that facilitates their purification. We used the phosphonate methyltransferase DhpI involved in dehydrophos biosynthesis to methylate a variety of phosphonate natural products in crude spent medium with a mixture of labeled and unlabeled S-adenosyl methionine. Mass-guided fractionation then allowed straightforward purification. We illustrate its utility by purifying a phosphonate that led to the identification of the fosfazinomycin biosynthetic gene cluster. This unusual natural product contains a hydrazide linker between a carboxylic acid and a phosphonic acid. Bioinformatic analysis of the gene cluster provides insights into how such a structure might be assembled. [ABSTRACT FROM AUTHOR]

This article outlines the process development leading to the manufacture of 800 g of BMS-986189, a macrocyclic peptide active pharmaceutical ingredient. Multiple N-methylated unnatural amino acids posed challenges to manufacturing due to the lability of the peptide to cleavage during global side chain deprotection and precipitation steps. These issues were exacerbated upon scale-up, resulting in severe yield loss and necessitating careful impurity identification, understanding the root cause of impurity formation, and process optimization to deliver a scalable synthesis. A systematic study of macrocyclization with its dependence on concentration and pH is presented. In addition, a side chain protected peptide synthesis is discussed where the macrocyclic protected peptide is extremely labile to hydrolysis. A computational study explains the root cause of the increased lability of macrocyclic peptide over linear peptide to hydrolysis. A process solution involving the use of labile protecting groups is discussed. Overall, the article highlights the advancements achieved to enable scalable synthesis of an unusually labile macrocyclic peptide by solid-phase peptide synthesis. The sustainability metric indicates the final preparative chromatography drives a significant fraction of a high process mass intensity (PMI).

Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides containing thioether rings. In addition to these cross-links, the clinical candidate lantibiotic NAI-107 also possesses a C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) and a unique 5-chloro-l-tryptophan (ClTrp) moiety linked to its potent bioactivity. Bioinformatic and genetic analyses on the NAI-107 biosynthetic gene cluster identified mibH and mibD as genes encoding flavoenzymes responsible for the formation of ClTrp and AviCys, respectively. The biochemical basis for the installation of these modifications on NAI-107 and the substrate specificity of either enzyme is currently unknown. Using a combination of mass spectrometry, liquid chromatography, and bioinformatic analyses, we demonstrate that MibD is an FAD-dependent Cys decarboxylase and that MibH is an FADH 2 -dependent Trp halogenase. Most FADH 2 -dependent Trp halogenases halogenate free Trp, but MibH was only active when Trp was embedded within its cognate peptide substrate deschloro NAI-107. Structural comparison of the 1.88-Å resolution crystal structure of MibH with other flavin-dependent Trp halogenases revealed that subtle amino acid differences within the MibH substrate binding site generates a solvent exposed crevice presumably involved in determining the substrate specificity of this unusual peptide halogenase.

Cytolysin, a two-component lanthipeptide comprising cytolysin S (CylL S ″) and cytolysin L (CylL L ″), is the only family member to exhibit lytic activity against mammalian cells in addition to synergistic antimicrobial activity. A subset of the thioether cross-links of CylL S ″ and CylL L ″ have ll stereochemistry instead of the canonical dl stereochemistry in all previously characterized lanthipeptides. The synthesis of a CylL S ″ variant with dl stereochemistry is reported. Its antimicrobial activity was found to be decreased, but not its lytic activity against red blood cells. Hence, the unusual ll stereochemistry is not responsible for the lytic activity., Competing Interests: Notes The authors declare no competing financial interest.

Lanthipeptides are natural products that belong to the family of ribosomally synthesized and post-translationally modified peptides (RiPPs). They contain characteristic lanthionine (Lan) or methyllanthionine (MeLan) structures that contribute to their diverse biological activities. Despite its structurally diverse set of 30 substrates, the highly substrate-tolerant lanthipeptide synthetase ProcM is shown to display high selectivity for formation of a single product from selected substrates. Mutation of the active site zinc ligands to alanine or the unique zinc ligand Cys971 to histidine resulted in a decrease of the cyclization rate, especially for the second cyclization of the substrates ProcA1.1, ProcA2.8, and ProcA3.3. Surprisingly, for ProcA3.3 these mutations also altered the regioselectivity of cyclization resulting in a new major product. ProcM was not able to correct the ring topology of incorrectly cyclized intermediates and products, suggesting that thermodynamic control is not operational. Collectively, the data in this study suggest that the high regioselectivity of product formation is governed by the selectivity of the initially formed ring.

Natural product discovery has been boosted by genome mining approaches, but compound purification is often still challenging. We report an enzymatic strategy for "stable isotope labeling of phosphonates in extract" (SILPE) that facilitates their purification. We used the phosphonate methyltransferase DhpI involved in dehydrophos biosynthesis to methylate a variety of phosphonate natural products in crude spent medium with a mixture of labeled and unlabeled S-adenosyl methionine. Mass-guided fractionation then allowed straightforward purification. We illustrate its utility by purifying a phosphonate that led to the identification of the fosfazinomycin biosynthetic gene cluster. This unusual natural product contains a hydrazide linker between a carboxylic acid and a phosphonic acid. Bioinformatic analysis of the gene cluster provides insights into how such a structure might be assembled., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)