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While traditional PHA production relies on refined carbon sources and pure cultures, high costs and scalability challenges limit commercial viability. Extremophiles, particularly halophiles, have emerged as promising candidates for cost-effective, large-scale production of PHAs. Their ability to thrive in extreme environments reduces contamination risks, minimizes the need for sterilization, and lowers operational costs. Advancements in metabolic engineering, synthetic biology, and CRISPR-based genome editing have enhanced PHA yields by optimizing metabolic flux and cell morphology. Additionally, utilizing alternative feedstocks such as biowaste, syngas, methane, and CO\u2082 improves economic feasibility. Next-generation industrial biotechnology integrates extremophilic microbes with AI-driven fermentation and eco-friendly downstream processing to enhance scalability. Industrial-scale production of PHAs using Halomonas spp. and other extremophiles demonstrates significant progress toward commercialization, paving the way for sustainable biopolymer applications in reducing plastic pollution<\/jats:p>","DOI":"10.3390\/polym17070853","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T08:42:35Z","timestamp":1742892155000},"page":"853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Toward Sustainable Polyhydroxyalkanoates: A Next-Gen Biotechnology Approach"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7892-2601","authenticated-orcid":false,"given":"Vipin Chandra","family":"Kalia","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-719X","authenticated-orcid":false,"given":"Rahul Vikram","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-6342","authenticated-orcid":false,"given":"Chunjie","family":"Gong","sequence":"additional","affiliation":[{"name":"Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-5301","authenticated-orcid":false,"given":"Jung-Kul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kalia, V.C., Patel, S.K.S., Karthikeyan, K.K., Jeya, M., Kim, I.W., and Lee, J.-K. 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