Metagenome-Informed Engineering of Monoclonal Antibodies: Mining Microbial Immunoglobulin-Like Domains for Ultra-Stable Therapeutics

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This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2026 | Volume : 16 | 01 | Page :
    By

    Atul Khajuria,

  • Ashish Kumar,

  1. Dean, University School of Allied and Health Care Sciences Rayat Bahra Professional University, VPO BOHAN, Tehsil &Distt. Hoshiarpur,, Punjab, 146001, India
  2. Assistant Professor, University School of Medical Laboratory Sciences Rayat Bahra Professional University, VPO BOHAN, Tehsil &Dist. Hoshiarpur, Punjab,146001, Punjab, IndiaMetagenomics; Monoclonal antibodies; Immunoglobulin-like domains; Protein engineering; Thermostability; Antibody stability; Microbial scaffolds; Biologics; Fc engineering; Synthetic biology

Abstract

Metagenome-informed engineering represents an emerging strategy for improving the stability and functionality of monoclonal antibodies (mAbs) by leveraging the vast diversity of microbial immunoglobulin-like (Ig-like) domains (10,24). These domains, derived from uncultured bacteria and bacteriophages, exhibit exceptional thermostability, protease resistance, and structural resilience due to adaptation to extreme environments (29,30). This review highlights advances in metagenomic mining, structural characterization, and protein engineering that enable the integration of microbial Ig-like scaffolds into antibody frameworks (24). Key engineering approaches, including CDR grafting, domain fusion, and de novo design, are discussed alongside preclinical validation methods and stability assays (4,10). The therapeutic potential of ultra-stable mAbs across oncology, infectious diseases, and autoimmune disorders is examined, with emphasis on improved pharmacokinetics and manufacturability (10,14). Challenges such as immunogenicity and regulatory considerations are also addressed, along with strategies for mitigation (10,11). Finally, the integration of artificial intelligence and synthetic biology is explored as a future direction for accelerating antibody design (24). Overall, metagenome-informed antibody engineering offers a transformative pathway toward developing next-generation biologics with enhanced stability, reduced cost, and broader global accessibility (10,24).

Keywords: Metagenomics; Monoclonal antibodies; Immunoglobulin-like domains; Protein engineering; Thermostability; Antibody stability; Microbial scaffolds; Biologics; Fc engineering; Synthetic biology

How to cite this article:
Atul Khajuria, Ashish Kumar. Metagenome-Informed Engineering of Monoclonal Antibodies: Mining Microbial Immunoglobulin-Like Domains for Ultra-Stable Therapeutics. Research and Reviews : A Journal of Biotechnology. 2026; 16(01):-.
How to cite this URL:
Atul Khajuria, Ashish Kumar. Metagenome-Informed Engineering of Monoclonal Antibodies: Mining Microbial Immunoglobulin-Like Domains for Ultra-Stable Therapeutics. Research and Reviews : A Journal of Biotechnology. 2026; 16(01):-. Available from: https://journals.stmjournals.com/rrjobt/article=2026/view=241312


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Ahead of Print Subscription Review Article
Volume 16
01
Received 19/03/2026
Accepted 27/04/2026
Published 29/04/2026
Publication Time 41 Days
18

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