A platform for distributed production of synthetic nitrated proteins in live bacteria

Butler, Neil D.; Sen, Sabyasachi; Brown, LC; Lin, Minwei; Kunjapur, Aditya M.

doi:10.1038/s41589-023-01338-x

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…In particular, bacterial strains with recoded genomes that minimize the side-effects of GCE have been successfully constructed, , and other genetically recoded organisms can be expected . Moreover, exogenous addition of AcK may become unnecessary in the near future due to the notable advances in ncAA biosynthesis. − Indeed, the biosynthesis of d -Cys-ε-Lys was recently achieved, and optimistically bioacetylation of lysine should be feasible. Besides AcK, other types of lysine acylation PTMs should work similarly in sirtuin-dependent T7RNAP design, and may even respond specifically to sirtuin subtypes .…”

Section: Discussionmentioning

confidence: 99%

A Sirtuin-Dependent T7 RNA Polymerase Variant

Wang,

Ji,

Sun

et al. 2023

ACS Synth. Biol.

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Transcriptional regulation is of great significance for cells to maintain homeostasis and, meanwhile, represents an innovative but less explored means to control biological processes in synthetic biology and bioengineering. Herein we devised a T7 RNA polymerase (T7RNAP) variant through replacing an essential lysine located in the catalytic core (K631) with N εacetyl-L-lysine (AcK) via genetic code expansion. This T7RNAP variant requires the deacetylase activity of NAD-dependent sirtuins to recover its enzymatic activities and thereby sustains sirtuindependent transcription of the gene of interest in live cells including bacteria and mammalian cells as well as in in vitro systems. This T7RNAP variant could link gene transcription to sirtuin expression and NAD availability, thus holding promise to support some relevant research.

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Section: Discussionmentioning

confidence: 99%

A Sirtuin-Dependent T7 RNA Polymerase Variant

Wang,

Ji,

Sun

et al. 2023

ACS Synth. Biol.

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“…By rewiring bacterial metabolism, we have created a bacterial strain that can autonomously produce nitrated forms of any user-defined recombinant antigen. 10 Our goal is to use these live attenuated bacteria as nitrated antigen producers and delivery vehicles to transport antigens directly to regions of infection or disease. Through this strategy, we intend to overcome two major limitations of current vaccination strategies – the lack of localized immune response and the inability to target cross-serotype or more generalized antigens.…”

Section: Nitro Biosciences: Next-generation Vaccines Enabled Via Nitr...mentioning

confidence: 99%

Nitro Biosciences:

Butler,

Kunjapur

2023

Delaware Journal of Public Health

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Novel modalities of vaccine will be required to address the current and future public health concerns we face. Many infectious diseases lack clinically approved vaccines causing immense burden to the health care system both domestically and abroad. More concerningly, the prevalence of antimicrobial resistance (AMR) is anticipated to rise over the coming decades and limit our tools to treat these infections. There is thus an urgent need to develop vaccinations to overcome these rising gaps in treatment and prevent infections moving forward. At Nitro Biosciences, we are developing a platform to create next-generation vaccines for diseases currently lacking clinically approved products. By harnessing an expanded genetic code, we can precisely modify antigens to enhance their immunogenicity, enabling a broadening of the scope of antigens to target in vaccine development and enhancing the potential to create efficacious vaccines where other efforts have failed.

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Cellular Site-Specific Incorporation of Noncanonical Amino Acids in Synthetic Biology

Niu,

Guo

2024

Chem. Rev.

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Over the past two decades, genetic code expansion (GCE)-enabled methods for incorporating noncanonical amino acids (ncAAs) into proteins have significantly advanced the field of synthetic biology while also reaping substantial benefits from it. On one hand, they provide synthetic biologists with a powerful toolkit to enhance and diversify biological designs beyond natural constraints. Conversely, synthetic biology has not only propelled the development of ncAA incorporation through sophisticated tools and innovative strategies but also broadened its potential applications across various fields. This Review delves into the methodological advancements and primary applications of sitespecific cellular incorporation of ncAAs in synthetic biology. The topics encompass expanding the genetic code through noncanonical codon addition, creating semiautonomous and autonomous organisms, designing regulatory elements, and manipulating and extending peptide natural product biosynthetic pathways. The Review concludes by examining the ongoing challenges and future prospects of GCE-enabled ncAA incorporation in synthetic biology and highlighting opportunities for further advancements in this rapidly evolving field.

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A platform for distributed production of synthetic nitrated proteins in live bacteria

Cited by 4 publications

References 56 publications

A Sirtuin-Dependent T7 RNA Polymerase Variant

A Sirtuin-Dependent T7 RNA Polymerase Variant

Nitro Biosciences:

Cellular Site-Specific Incorporation of Noncanonical Amino Acids in Synthetic Biology

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