Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health

TIAN Yingru; HUANG Xiaoyun; DAO Jinwei; LI Yuehao; XU Tao; YANG Hui; WAN Dandan; WEI Daixu

doi:10.12211/2096-8280.2025-059

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Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health

Invited Review | 更新时间：2026-01-15

- Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health
- Synthetic Biology Journal Vol. 6, Issue 6, Pages: 1332-1348(2025)
- 作者机构：
  
  1.曲靖健康医学院，云南曲靖 655100
  2.德宏师范学院德宏生物医药工程研究中心，云南德宏 678400
  3.成都大学临床医学院与附属医院，四川成都 610106
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-059
  CLC： TQ323.4;Q503;R318.08;R329;X171.5
- Received：12 June 2025，
  
  Revised：2025-11-04，
  
  Published：31 December 2025
- 稿件说明：
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田英入，黄晓云，刀金威，李玥昊，徐涛，杨辉，万丹丹，魏岱旭. 医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展［J］. 合成生物学， 2025， 6（6）： 1332-1348

TIAN Yingru， HUANG Xiaoyun， DAO Jinwei， LI Yuehao， XU Tao， YANG Hui， WAN Dandan， WEI Daixu. Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health［J］. Synthetic Biology Journal， 2025， 6（6）： 1332-1348
田英入，黄晓云，刀金威，李玥昊，徐涛，杨辉，万丹丹，魏岱旭. 医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展［J］. 合成生物学， 2025， 6（6）： 1332-1348 DOI： 10.12211/2096-8280.2025-059.

TIAN Yingru， HUANG Xiaoyun， DAO Jinwei， LI Yuehao， XU Tao， YANG Hui， WAN Dandan， WEI Daixu. Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health［J］. Synthetic Biology Journal， 2025， 6（6）： 1332-1348 DOI： 10.12211/2096-8280.2025-059.

摘要

聚羟基脂肪酸酯（PHA）是一类具有生物相容性、生物可降解性以及优良材料学性能的生物合成聚酯，在医药领域展现出巨大的应用潜力。然而，产能低限制了PHA的应用。近年来，合成生物技术的发展为PHA的优化生产提供了新途径。本文综述了PHA作为医用材料的优势，包括单体多样性、可控降解性及优异的生物相容性；探讨了合成生物技术在PHA生产中的应用，如CRISPR/Cas工具、启动子工程、RBS优化、微生物细胞形态工程、染色体整合技术等策略，这些策略可优化合成途径和提高产量，并且推动工业化制备医用级PHA的进展。并进一步阐述了医用级PHA近些年在骨修复、皮肤再生、心血管工程等领域取得的显著应用成果。未来，融合多学科创新有望突破PHA的技术壁垒，使其成为生物医用材料领域的核心选项，推动再生医学的发展。

Abstract

Polyhydroxyalkanoates (PHAs) represent a versatile class of microbial polyesters with exceptional biocompatibility

tunable biodegradability

and a broad range of mechanical and chemical properties. These characteristics make PHA highly suitable for diverse biomedical applications

including tissue engineering scaffolds

targeted drug delivery systems

wound dressings

and implantable devices. Notably

PHA degradation products such as 3-hydroxybutyrate are endogenous metabolites

which minimizes immunogenic responses and enhances long-term biocompatibility compared to conventional synthetic polymers. Recent advances in synthetic biology have significantly improved PHA biosynthesis. Metabolic engineering strategies

including CRISPR/Cas9-mediated genome editing for redirecting carbon flux toward PHA accumulation

CRISPR interference for modulating competing pathways

and optimization of promoter and ribosome-binding site (RBS) libraries

have enabled precise control over monomer composition and polymer properties. Additionally

microbial morphological engineering such as FtsZ-targeted cell elongation has been used to increase intracellular PHA content to over 90% of cellular dry weight. These developments have facilitated the synthesis of tailored PHA variants

ranging from rigid poly(3-hydroxybutyrate) (PHB) to elastomeric poly(3-hydroxybutyrate-

-4-hydroxybutyrate) (P34HB). Medical-grade PHA has shown significant translational potential across multi

ple therapeutic domains. Injectable porous microspheres composed of poly(3-hydroxybutyrate-

-3-hydroxyvalerate-

-3-hydroxyhexanoate) (PBVHx) have been developed for minimally invasive bone regeneration. Electrospun P34HB scaffolds exhibit simultaneous antibacterial and pro-angiogenic activities

accelerating wound healing. PHA-based nanocarriers enable sustained drug release for Alzheimer's disease and systemic lupus erythematosus treatment. Furthermore

virus-mimetic PHA particles have been exploited as adjuvant systems to enhance antigen presentation in tuberculosis and COVID-19 vaccine platforms. Future perspectives highlight the convergence of synthetic biology

materials science

and clinical translation to fully realize PHA’s biomedical potential. Next-generation industrial biotechnology (NGIB)

which uses halophilic microorganisms for continuous fermentation under open conditions combined with advanced downstream purification protocols

is expected to improve the scalability and accessibility of medical-grade PHA. Integration with emerging technologies such as 3D bioprinting and organoid culture systems will expand PHA’s utility in complex

patient-specific tissue engineering applications. Collectively

these advances establish PHA as a highly promising foundational biomaterial platform for next-generation regenerative medicine and targeted therapeutic strategies.

关键词

Keywords

references

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