Summary
Interesting optical and photochemical properties make microbial rhodopsin a promising biological material suitable for various applications, but the cost‐prohibitive nature of production has limited its commercialization. The aim of this study was to explore the natural biodiversity of Indian solar salterns to isolate natural bacteriorhodopsin (
BR
) variants that can be functionally expressed in
Escherichia coli
. In this study, we report the isolation, functional expression and purification of
BR
s from three pigmented haloarchaea, wsp3 (water sample Pondicherry), wsp5 and K1
T
isolated from two Indian solar salterns. The results of the 16S
rRNA
data analysis suggest that wsp3, wsp5 and K1
T
are novel strains belonging to the genera
Halogeometricum, Haloferax and Haloarcula
respectively. Overall, the results of our study suggest that 17 N‐terminal residues, that were not included in the gene annotation of the close sequence homologues, are essential for functional expression of
BR
s. The primary sequence, secondary structural content, thermal stability and absorbance spectral properties of these recombinant
BR
s are similar to those of the previously reported
Haloarcula marismortui
Hm
BRI
. This study demonstrates the cost‐effective, functional expression of
BR
s isolated from haloarchaeal species using
E. coli
as an expression host and paves the way for feasibility studies for future applications.
Abnormal proliferation and disrupted differentiation of hematopoietic progenitors mark leukemia. Histone cell cycle regulator A (HIRA), a histone chaperone, regulates hemogenic to hematopoietic transition involved in normal hematopoiesis. But, its role remains unexplored in leukemia, a case of dysregulated hematopoiesis. Here, the Cancer Cell Line Encyclopedia database analysis showed enhanced HIRA mRNA expression in cells of hematopoietic and lymphoid origin with maximal expression in the chronic myeloid leukemia (CML) cell line, K562. This observation was further endorsed by the induced expression of HIRA in CML patient samples compared to healthy individuals and Acute Myeloid Leukemia patients. Downregulation of HIRA in K562 cells displayed cell cycle arrest, loss in proliferation, presence of polyploidy with significant increase in CD41+ population thereby limiting proliferation but inducing differentiation of leukemia cells to megakaryocyte fate. Induced megakaryocyte differentiation of mouse Hira‐knockout hematopoietic progenitors in vivo further confirmed the in vitro findings in leukemia cells. Molecular analysis showed the involvement of MKL1/GATA2/H3.3 axis in dictating differentiation of CML cells to megakaryocytes. Thus, HIRA could be exploited for differentiation induction therapy in CML and in chronic pathological conditions involving low platelet counts.
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