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Psychrophiles can be defined as the members of the kingdom Monera thriving permanently at the lowest temperature range. Since the majority of our planet is generally cold, psychrophiles are common within a wide range of habitats. Extensive research in the field of genomics, transcriptomics, and proteomics revealed that psychrophiles are endowed with several adaptive features to survive and grow in their cold habitat. Several adaptations in different cellular entities, such as cell envelopes, enzymes, chaperones; protein synthesis machinery, energy generating system, and metabolic pathways have been reported. All these modifications in psychrophiles are found to be indispensable to withstand these harsh environmental challenges. The chapter focuses on the current state of knowledge for understanding the biodiversity and mechanism of low-temperature adaptation of psychrophilic microorganisms. Furthermore, the modified biomolecules in psychrophiles, mainly enzymes and reserved materials, with distinct features, were found to be useful for several applications including molecular biology research, bioremediation, detergent formulations, and the food industry. The biotechnological and industrial significance of the psychrophiles is also discussed in this chapter.&nbsp

Leishmania has a remarkable ability to proliferate under widely fluctuating levels of essential nutrients, such as glucose. For this, the parasite is heavily dependent on its gluconeogenic machinery. One perplexing aspect of gluconeogenesis in Leishmania is the lack of the crucial gene for pyruvate carboxylase (PC). PC-catalyzed conversion of pyruvate to oxaloacetate is a key entry point through which gluconeogenic amino acids are funneled into this pathway. The absence of PC in Leishmania thus raises question about the mechanism of pyruvate entry into the gluconeogenic route. In the present study, we report that this task is accomplished in Leishmania major through a novel functional partnership between its mitochondrial malic enzyme (LmME) and carbonic anhydrase 1 (LmCA1). Using a combination of pharmacological inhibition studies with genetic manipulation, we show that both of these enzymes are necessary for promoting gluconeogenesis and supporting parasite growth under glucose-limiting conditions. Functional cross-talk between LmME and LmCA1 was evident when it was observed that the growth retardation caused by inhibition of any one of these enzymes could be protected to a significant extent by overexpressing the other enzyme. We also found that, although LmCA1 exhibited constitutive expression, the LmME protein level was strongly upregulated under low glucose conditions. Notably, both LmME and LmCA1 were found to be important for survival of Leishmania amastigotes within host macrophages. Taken together, our results indicate that LmCA1 by virtue of its CO2 concentrating ability stimulates LmME-catalyzed pyruvate carboxylation, thereby driving gluconeogenesis through the pyruvate-malate-oxaloacetate bypass pathway. Additionally, our study establishes LmCA1 and LmME as promising therapeutic targets.

Leishmaniahas a remarkable ability to proliferate under widely fluctuating levels of essential nutrients, such as glucose. For this the parasite is heavily dependent on its gluconeogenic machinery. One perplexing aspect of gluconeogenesis inLeishmaniais the lack of the crucial pyruvate carboxylase (PC) gene. PC-catalyzed conversion of pyruvate to oxaloacetate is a key entry point through which gluconeogenic amino acids are funnelled into this pathway. Absence of PC inLeishmaniathus raises question about the mechanism of pyruvate entry into the gluconeogenic route. We report here that this task is accomplished inLeishmania majorthrough a novel functional partnership between its mitochondrial malic enzyme (LmME) and cytosolic carbonic anhydrase (LmCA1). Using a combination of pharmacological inhibition studies with genetic manipulation, we showed that both these enzymes are necessary in promoting gluconeogenesis and supporting parasite growth under glucose limiting condition. Functional crosstalk between LmME and LmCA1 was evident when it was observed that the growth retardation caused by inhibition of any one of these enzymes could be protected to a significant extent by overexpressing the other enzyme. We also found that while LmCA1 exhibited constitutive expression, LmME protein level was strongly upregulated in low glucose condition. Notably, both LmME and LmCA1 were found to be important for survival ofLeishmaniaamastigotes within host macrophages. Taken together, our results indicate that LmCA1 by virtue of its CO2concentrating ability stimulates LmME-catalyzed pyruvate carboxylation, thereby driving gluconeogenesis through pyruvate-malate-oxaloacetate bypass pathway. Additionally, our study establishes LmCA1 and LmME as promising therapeutic targets.