Review Litter to Leaf: The Unexplored Potential of Silk Byproducts Roopa Reddy , 1,6 Qiuran Jiang , 2,3 Pornanong Aramwit , 4,5,7 and Narendra Reddy , 1,8, * Silk has remained the most preferred protein fiber since its discovery in 3000 BC. However, the cost, availability, and resources required to rear the silkworms and process silk are imposing considerable constraints on the future of silk. It is often unrealized that apart from the fibers, production and processing of silk are a source for a diverse range of sustainable, biodegradable, and biocompatible polymers. Hence, delineating itself from being the primary source of protein fibers for millenniums, the silk industry worldwide is transitioning into a biobased industry and as a source for pharmaceuticals, biomaterials, cosmetics, food, and energy. Toward this, byproducts (BPs) and co-products (CPs) that are inevitably generated are now being considered to be of immense economic value and could be up to 10 times more valuable than the silk fibers. Here, we elucidate the properties and potential applications of silk BPs and CPs to present the true potential of silkworms and to promote the establishment of silkworm- based bioeconomy and biorefineries. Silk beyond the Fibers Although discovered accidentally in China, the journey of silk has been fascinating and silk has played an important role in the social and economic status and political implications across the globe for more than 5000 years. Treasured for its elegance and unparalleled virtues, silk and silk products have graced the royals and the commons equally. Silk has been one of the most traded textile materials and continues to play a crucial role in the geopolitical events even today. Despite only two countries (China and India) and one species of silkworm (Bombyx mori; Box 1) producing more than 90% of the world’s silk fibers, silk-based products are exten- sively used worldwide not only for apparel and textiles but also for medical and other applications. Throughout its history, considerable technical, economical, and social challenges have been overcome to ensure the legacy and importance of silk. However, the focus of the silk industry has been to rise production of silk, decrease costs, and develop exquisite products and increase the applicability and acceptance of silk. Although the dominance of silk as a preferred fiber con- tinues, silk and silk industries face numerous challenges. Increasing costs, issues in quality, changing climatic conditions, and constraints in availability of resources are imposing unseen restrictions on the rearing (see Glossary), production, processing, and selling of silk and silk products. There has been considerable decrease in the growth and value addition of silk and silk goods in the last decade or so. To overcome these challenges, the silk industry is actively seeking new avenues of expanding beyond fibers and fibrous applications. It is often unrealized that the cultivation and processing of silk generates several unique and highly valuable byproducts (BPs) and co-products (CPs; Figure 1, Key Figure) at each stage of pro- cessing. The nearly 25% of sericin glue proteins in the extruded fibers that has to be removed through degumming before silk can be used, the worms (pupae) which typically are equivalent to the weight of the cocoon, the remnants of the leaves left over after consumption by the insects, and even the excreta of the insects are all inevitably generated. It is also interesting to note that Highlights Silkworms are biofactories that generate proteins, lipids, and polysaccharides. Sericin, pupae, litter, and mulberry leaves contain valuable biomolecules. The values of these biomolecules could be three to five times the value of silk fibers. Proteins in pupae and litter show anti- cancer and antiviral activities. In the future, silkworms could be reared for their immensely valuable byproducts rather than their fiber-producing cocoons. 1 Center for Incubation, Innovation, Research and Consultancy, Jyothy Institute of Technology, Thataguni Post, Bengaluru 560082, Karnataka, India 2 Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai 201620, China 3 College of Textiles, Donghua University, Shanghai 201620, China 4 Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences and Center of Excellence in Bioactive Resources for Innovative Clinical Applications, Chulalongkorn University, Bangkok, Thailand 10330 5 The Academy of Science, The Royal Society of Thailand, Dusit, Bangkok, Thailand 10330 6 https://ciirc.res.in/cell-and-molecular- biology/ 7 http://www.pharm.chula.ac.th/dept7/ index.php?main_id=3&sub_id=3&staff_ id=6 8 https://ciirc.res.in/biopolymers-and- biocomposites/ *Correspondence: narendra.r@ciirc.jyothyit.ac.in (N. Reddy). Trends in Biotechnology, Month 2020, Vol. xx, No. xx https://doi.org/10.1016/j.tibtech.2020.11.001 1 © 2020 Elsevier Ltd. All rights reserved. Trends in Biotechnology TIBTEC 2011 No. of Pages 13