Biocatalytic reduction of nitro-sulfonamides: enzyme engineering, process integration, and sustainable pathways to p-aminobenzenesulfonamide.

Authors

Rui Ai, Noor Muhammad, Yuelong Cui, Liqiang Wang, Yao Wang, Shaoting Weng, Mohib Ullah Kakar, Suliman Khan, Sajjad Ahmad

Published in

Frontiers in bioengineering and biotechnology. Volume 14. Pages 1867973. Epub Jul 20, 2026.

Abstract

Sulfonamides remain important to medicinal and fine-chemical production but conventional aniline precursor routes like Pd-catalysed hydrogenation and Béchamp reductions carry sustainability, safety, and chemoselectivity challenges, especially for N-S bond integrity. This review assesses biocatalytic nitroreduction as a selective alternative for nitro-sulfonamides, focusing on p-aminobenzenesulfonamide (p-ABS). We summarise mechanistic and engineering advances in Type I (oxygen-insensitive) flavin-dependent nitroreductases (NTRs), highlight emerging roles and limits of Old Yellow Enzymes, and discuss auxiliary reductive platforms (H₂-driven hydrogenases, photo-/electro-biocatalysis) for improved cofactor economy and endpoint selectivity. Process-intensification strategies, whole-cell vs. cell-free operation, immobilisation, packed-bed flow, on-line LC/IR PAT, and NAD(P)H regeneration via GDH/FDH or electroenzymatic modules are mapped to chemoselectivity risks (hydroxylamine accumulation, azo/azoxy formation) and mass-transfer constraints. We highlight development choices with green metrics (PMI, E-factor) and emphasise early LCA integration to avoid burden shifting from buffer salts or mediator residues. Evidence from continuous NTR reactors and immobilised formats supports scalable, aqueous, low-pressure operation; however, direct data on sulfonamide-linked nitroarenes is limited. This motivates a feasibility screen using an NTR panel (including engineered NfsB lineages), water-rich media with low co-solvent, and O₂-tolerant settings. We conclude with a proposed flowsheet for p-ABS coupling immobilised NTR with FDH or electro-NAD(P)H supply, real-time analytics, and membrane-based product extraction. As direct data on sulfonamide-linked nitroarenes remain limited, this roadmap provides a practical and critical starting point for substrate-specific feasibility screening and future development.

PMID:
42548832
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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