From carbon dioxide to starch: no plants required: Many plants turn glucose from photosynthesis into polymers that form insoluble starch granules ideal for long-term energy storage in roots and seeds. Cai et al . developed a hybrid system in which carbon dioxide is reduced to methanol by an inorganic catalyst and then converted by enzymes first to three and six carbon sugar units and then to polymeric starch. This artificial starch anabolic pathway relies on engineered recombinant enzymes from many different source organisms and can be tuned to produce amylose or amylopectin at excellent rates and efficiencies relative to other synthetic carbon fixation systems—and, depending on the metric used, even to field crops. —MAF

Acetyl-CoA is a fundamental metabolite for all life on Earth, and is also a key starting point for the biosynthesis of a variety of industrial chemicals and natural products. Here we design and construct a Synthetic Acetyl-CoA (SACA) pathway by repurposing glycolaldehyde synthase and acetyl-phosphate synthase. First, we design and engineer glycolaldehyde synthase to improve catalytic activity more than 70-fold, to condense two molecules of formaldehyde into one glycolaldehyde. Second, we repurpose a phosphoketolase to convert glycolaldehyde into acetyl-phosphate. We demonstrated the feasibility of the SACA pathway in vitro, achieving a carbon yield ~50%, and confirmed the SACA pathway by ¹³C-labeled metabolites. Finally, the SACA pathway was verified by cell growth using glycolaldehyde, formaldehyde and methanol as supplemental carbon source. The SACA pathway is proved to be the shortest, ATP-independent, carbon-conserving and oxygen-insensitive pathway for acetyl-CoA biosynthesis, opening possibilities for producing acetyl-CoA-derived chemicals from one-carbon resources in the future.

The flavonoid extract fromErigeron breviscapus, breviscapine, has increasingly been used to treat cardio- and cerebrovascular diseases in China for more than 30 years, and plant supply ofE. breviscapusis becoming insufficient to satisfy the growing market demand. Here we report an alternative strategy for the supply of breviscapine by building a yeast cell factory using synthetic biology. We identify two key enzymes in the biosynthetic pathway (flavonoid-7-O-glucuronosyltransferase and flavone-6-hydroxylase) fromE. breviscapusgenome and engineer yeast to produce breviscapine from glucose. After metabolic engineering and optimization of fed-batch fermentation, scutellarin and apigenin-7-O-glucuronide, two major active ingredients of breviscapine, reach to 108 and 185 mg l^–1, respectively. Our study not only introduces an alternative source of these valuable compounds, but also provides an example of integrating genomics and synthetic biology knowledge for metabolic engineering of natural compounds.

Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

Medicinal plants represent a huge reservoir of secondary metabolites (SMs), substances with significant pharmaceutical and industrial potential. However, obtaining secondary metabolites remains a challenge due to their low-yield accumulation in medicinal plants; moreover, these secondary metabolites are produced through tightly coordinated pathways involving many spatiotemporally and environmentally regulated steps. The first regulatory layer involves a complex network of transcription factors; a second, more recently discovered layer of complexity in the regulation of SMs is epigenetic modification, such as DNA methylation, histone modification and small RNA-based mechanisms, which can jointly or separately influence secondary metabolites by regulating gene expression. Here, we summarize the findings in the fields of genetic and epigenetic regulation with a special emphasis on SMs in medicinal plants, providing a new perspective on the multiple layers of regulation of gene expression. Graphical Abstract

Plant natural products (PNPs) are the main sources of drugs, food additives, and new biofuels and have become a hotspot in synthetic biology. In the past two decades, the engineered biosynthesis of many PNPs has been achieved through the construction of microbial cell factories. Alongside the rapid development of plant physiology, genetics, and plant genetic modification techniques, hosts have now expanded from single-celled microbes to complex plant systems. Plant synthetic biology is an emerging field that combines engineering principles with plant biology. In this review, we introduce recent advances in the biosynthetic pathway elucidation of PNPs and summarize the progress of engineered PNP biosynthesis in plant cells. Furthermore, a future vision of plant synthetic biology is proposed. Although we are still a long way from overcoming all the bottlenecks in plant synthetic biology, the ascent of this field is expected to provide a huge opportunity for future agriculture and industry.