Although poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is the most promising biopolymer for petroleum-based plastics replacement, the low processes productivity as well as the high sale price represent a major barrier for its widespread usage. The present work examines comparatively the existing methods to enhance the yield of the PHBV co-polymer biologically produced and/or reduce their costs. The study is addressed to researchers working on the development of new biological production methods and/or the improvement of those currently used. At this aim, the authors have considered the analysis of some crucial aspects related to substrates and microorganism’s choice. The production strategies have been individuated, presented and discussed, either based on a single aspect (type of substrate or microorganism) or based on combined aspects (type of substrate and microorganism). Process operating conditions have been discussed as well. The analysis indicates that the addition of 3HV precursors is capable to dramatically enhance the hydroxyvalerate fraction in the produced biopolymers. On the other hand, due to the high costs of the 3HV precursors, the utilization of wild bacterial species capable to produce the hydroxyvalerate fraction from unrelated carbon sources (i.e. no 3HV precursors) also can be considered a valuable strategy for costs reduction. Moreover, metabolic engineering techniques can be successfully used to promote 3HV precursors-independent biosynthesis pathways and enhance the process productivity. The use of mixed cultures or extremophile bacteria avoids the need of sterile working conditions, and therefore favours the process scale-up. The utilization of the organic waste as substrate plays a key role for a sharp reduction of production costs. Finally, the selection of the most suitable substrate-microorganism combination cannot be separated by the adoption of an appropriate choice of reactor configuration and abiotic factors.

Graphic abstract

中文翻译：

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改进聚（3-羟基丁酸酯-co-3-羟基戊酸酯）（PHBV）共聚物的生物生产：一项重要评论

虽然聚（3-羟基丁酸酯-co-3-羟基戊酸酯（PHBV）是用于石油基塑料替代的最有前途的生物聚合物，其低生产效率以及较高的销售价格是其广泛使用的主要障碍。本工作比较地研究了现有方法，以提高生物生产的PHBV共聚物的收率和/或降低其成本。该研究针对从事新型生物生产方法开发和/或当前使用的生产方法改进的研究人员。为此，作者考虑了对与底物和微生物选择有关的一些关键方面的分析。基于单个方面（底物或微生物的类型）或基于组合方面（底物和微生物的类型）对生产策略进行了个性化，呈现和讨论。还讨论了过程操作条件。分析表明，添加3HV前体能够显着提高生产的生物聚合物中的羟基戊酸酯含量。另一方面，由于3HV前体的高成本，利用能够从无关碳源生产羟基戊酸酯级分的野生细菌物种（即没有3HV前体）的利用，也可以被认为是降低成本的有价值的策略。此外，代谢工程技术可以成功地用于促进独立于3HV前体的生物合成途径并提高过程生产率。混合培养物或极端微生物的使用避免了无菌工作条件的需要，因此有利于工艺规模的扩大。利用有机废物作为底物对于大幅降低生产成本起着关键作用。最后，最合适的衬底-微生物组合的选择不能被采用的反应器结构和非生物因素的适当选择的分离。

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