a College of Pharmaceutical Sciences, Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control , Southwest University , Chongqing , PR China.
b William G. Lowrie Department of Chemical and Biomolecular Engineering , The Ohio State University , Columbus , OH , USA.
Crit Rev Biotechnol. 2019 May;39(3):408-421. doi: 10.1080/07388551.2019.1571008. Epub 2019 Feb 10.
Some microorganisms naturally produce β-poly(l-malic acid) (PMA), which has excellent water solubility, biodegradability, and biocompatibility properties. PMA has broad prospective applications as novel biopolymeric materials and carriers in the drug, food, and biomedical fields. Malic acid, a four-carbon dicarboxylic acid, is widely used in foods and pharmaceuticals, as a platform chemical. Currently, malic acid produced through chemical synthesis and is available as a racemic mixture of l- and d-forms. The d-form malic acid exhibits safety concerns for human consumption. There is extensive interest to develop economical bioprocesses for l-malic acid and PMA production from renewable biomass feedstocks. In this review, we focus on PMA biosynthesis by Aureobasidium pullulans, a black yeast with a large genome containing genes encoding many hydrolases capable of degrading various plant materials. The metabolic and regulatory pathways for PMA biosynthesis, metabolic engineering strategies for strain development, process factors affecting fermentation kinetics and PMA production, and downstream processing for PMA recovery and purification are discussed. Prospects of microbial PMA and malic acid production are also considered.
有些微生物自然会产生 β-聚（L-苹果酸）（PMA），它具有极好的水溶性、生物降解性和生物相容性。PMA 作为新型生物聚合物材料和药物、食品和生物医学领域的载体具有广阔的应用前景。苹果酸是一种四碳二元羧酸，广泛应用于食品和制药行业，是一种平台化学品。目前，苹果酸是通过化学合成生产的，并且以 l-和 d-形式的外消旋混合物形式存在。d-形式的苹果酸对人类食用存在安全隐患。因此，人们广泛关注开发经济的生物工艺，从可再生生物质原料生产 L-苹果酸和 PMA。在这篇综述中，我们重点介绍了出芽短梗霉 Aureobasidium pullulans 生产 PMA，该菌是一种黑色酵母，基因组较大，包含许多能够降解各种植物材料的水解酶基因。讨论了 PMA 生物合成的代谢和调控途径、用于菌株开发的代谢工程策略、影响发酵动力学和 PMA 生产的过程因素、以及 PMA 回收和纯化的下游处理。还考虑了微生物 PMA 和苹果酸生产的前景。
