Biology subjects

Afzal, M. X.

Publications and source records attributed to Afzal, M. X..

2 recordsLinked to original sources

bioRxiv2025

Reduced carbon emissions and chain elongation during mixotrophic fermentation of a biomass feedstock

Anaerobic fermentation of biomass feedstocks using open cultures is a promising technology to produce platform carboxylates. Syngas, a mixture of H2, CO2, and CO, can be sourced sustainably and used to supplement biomass feedstocks as a source of acetyl-CoA, an intermediate for carboxylate chain elongation. To test this, syngas and corn silage were provided to a 10-L semi-continuous fermenter for 209 days of operation in a first-of-a-kind study at this scale. After acclimation to syngas, a two-fold reduction in average CO2 production rate (0.097 vs. 0.21 g L-1d-1) was observed over a period of 42 days in comparison to a control. Syngas co-feeding also increased average production rates of n-butyrate (C4) and n-caproate (C6) by 74% and 27%, respectively, although these effects were observed at relatively low C6 concentrations up to 4 g L-1. Relative abundances of Megasphaera and Dialister showed significant correlation (p<0.05) to consumption of H2 and CO as well as production of C4 and C6, suggesting involvement of these genera in mixotrophic metabolism. A feasibility analysis showed that syngas recirculation could return additional 1.54 USD m-3broth while costing 1.26 USD m-3broth and avoiding 1.81 kg CO2 eq. m-3broth in emissions compared to heterotrophic fermentation. We propose mixotrophic fermentation as a low-tech technology to turn fermenters into decentralized industrial carbon sinks. SYNOPSISFermentation of biomass and syngas could be used for sustainable and circular chemical production. This study tested the feasibility of this technology and identified relevant process parameters and microbial genera.

bioengineering↗

bioRxiv2025

Colorectal cancer-associated PCBP1 mutations disrupt protein stability in a dominant negative manner

Mutations in RNA-binding proteins are increasingly identified in cancers through tumor sequencing and are correlated with disease progression, therapy response, and overall patient outcomes, underscoring the need to study them. Here, we focus on the RNA-binding protein Poly-C binding protein 1 (PCBP1), which binds target RNAs through K-homology (KH) domains to regulate RNA fate. PCBP1 is a tumor suppressor gene and hotspot missense mutations at leucine residues 100 and 102 are observed in colorectal cancer (CRC). PCBP1 mutations have been recurrently reported in CRC genome-wide mutation studies and are associated with poor clinical outcomes; however, their effects on PCBP1 expression and function remain largely unexplored. We show that cancer-associated mutations substituting leucine 100 and 102 with glutamine, proline, or arginine destabilize PCBP1, leading to increased protein turnover. The L100/L102 residues occur at the interface of the RNA-binding KH1 and KH2 domains, and our molecular dynamics simulations show that mutations at these residues disrupt the secondary structure of PCBP1. Additionally, these mutants display increased cytoplasmic localization. Importantly, mutant PCBP1 physically interacts with wild type PCBP1 and suppresses its expression through a dominant-negative mechanism. Together, our data demonstrate that CRC-associated PCBP1 mutations destabilize the protein and act as dominant-negative variants, revealing a novel mechanism of tumor suppressor inactivation in colorectal cancer.

cancer biology↗